Regio- and diastereoselective synthesis of thioxothiazolidin- indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles

Regio- and diastereoselective synthesis of thioxothiazolidin- indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Regio- and diastereoselective synthesis of thioxothiazolidin- indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles Bagher Aghamiri, F. Matloubi Moghaddam, Sara Badpa, Leila Kavoosi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4306039/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jun, 2024 Read the published version in Scientific Reports → Version 1 posted 13 You are reading this latest preprint version Abstract In this publication, we reported a regio-, diastereoselective, and kinetically controlled reaction for synthesizing thioxothiazolidin-indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles. Obtaining only the kinetic thioxothiazolidin-indolin-2-one products together with their straightforward conversion to dispirocyclopentanebisoxindoles, excellent regio- and diastereoselectivity, easy reaction workup, and one-pot synthetic operation are considerable advantages of this work. Biological sciences/Drug discovery Physical sciences/Chemistry Regio- and diastereoselectivity kinetically controlled reaction thioxothiazolidin-indolin-2-ones dispirocyclopentanebisoxindoles oxoindolin-carbamodithioate hybrids Figures Figure 1 1. Introduction 3-Alkenyl-oxindoles are pharmacologically advantageous scaffolds that have many biological properties. The widespread occurrence of 3-alkenyl-oxindoles at the heart of many plant-based alkaloids and natural products has further reinforced their merit in organic and medicinal chemistry. 1–5 In recent decades, 3-alkenyl oxindoles have been widely investigated, and detailed works have been done for transforming 3-alkenyl oxindoles into novel functionalized heterocycles. 6–10 For instance, very recently, Li et al. described a procedure for the construction of sp 2 C–N bond between 3-alkenyl oxindoles and indazole/benzotriazole. 11 In 2023, Mainkar et al. reported proline-catalyzed diastereoselective synthesis of dihydroquinolinyl-spirooxindole via aza-Michael/aldol reaction of 3-alkenyl oxindole. 12 In 2023, Song and coworkers described the synthesis of 3-alkenyl-2-oxindoles via a transition-metal-free [4 + 1] cyclization pathway. 13 Again in 2023, Stephan et al. developed a metal-free, B(C 6 F 5 ( 3 catalyzed cyclopropanation of 3-alkenyl-oxindoles with diazomethanes. 14 Copper-catalyzed hydroboration of these compounds was also reported by Moro and coworkers. 15 According to other reports, 3-alkenyl oxindoles could easily converted to dispirooxindoles. 16–21 For example, the synthesis of dispirocyclopentanebisoxindoles via sequential Michael-aldol reaction of 3-alkenyl oxindoles was reported by Yan and coworkers. 22 As another example, very recently our research group described a facile reaction for transforming 3-alkenyl oxindoles to dispirocyclopentanebisoxindoles. 23 On the other hand, from the distant past to the present, S-heterocycles have maintained their importance as an essential part and core of FDA-approved drugs and medicinally active molecules. A straightforward approach to synthesizing S-heterocycles is exploiting dithiocarbamates. 24–25 The great nucleophilic strength of dithiocarbamates has made them widely used in organic transformations. For example, Alizadeh and coworkers reported a thermodynamic approach for synthesizing 2’,3’-dihydro-2’-thioxospiro[indole-3,6’-[1,3]-thiazin]-2(1 H )-ones derivatives using dithiocarbamates at reflux conditions. 26 Unexpectedly, when we checked the above reaction at room temperature, we found that the final products are completely different from the previous work, and at room temperature, the reaction seems to be under kinetic control that leads to the formation of novel thioxothiazolidin-indolin-2-ones molecules. In addition to this, we found that the final products (thioxothiazolidin-indolin-2-ones) easily convert to dispirocyclopentanebisoxindoles under basic conditions, the same as 3-alkenyl oxindoles and our previous work (Scheme 1). As a result of what we have mentioned above, in this publication, we would like to report a kinetically controlled reaction for synthesizing novel thioxothiazolidin-indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion to dispirocyclopentanebisoxindoles. This synthetic procedure provides a feasible approach for synthesizing novel organic molecules bearing oxindole cores that might have future medicinal applications and the obtained molecules could be suitable for drug screening. Scheme1. A comparative overview of the employed synthetic process in the previous and this work 2. Results and discussion Initially, we investigated the four-component reaction of N -allyl isatin 1a , phosphonium ylide 2 , carbon disulfide, and methylamine as the model reaction ( Table 1 ). Thus, a mixture of 1 (0.3 mmol), 2 (0.3 mmol) in EtOH (2.0 mL) was mixed and stirred at room temperature for 30 min, then methylamine (0.3 mmol) and carbon disulfide (0.3 mmol) were added and stirred for more 1.5 h to afford 1-allyl-4-hydroxy-3-methyl-4-phenyl-2-thioxothi- azolidin-5-yl)indolin-2-one ( 3a ) in satisfactory yield. Then, several solvents were assessed to achieve the optimal reaction conditions. The reaction proceeded slowly in DMSO, CHCl 3 , CH 3 CN, and CH 2 Cl 2 with unsatisfactory yield ( Table 1, entries 1-4 ). Furthermore, the reaction failed to occur in H 2 O and THF ( Table 1, entries 5, 6 ). In complete contrast, the reaction yield increased greatly in alcoholic solvents such as n-Octanol, MeOH, and PrOH, especially in EtOH ( Table 1, entries 7-12 ). PEG-400 was not as good as alcoholic solvents ( Table 1, entry 10 ). We found that the reaction proceeded well under catalyst-free conditions and at room temperature. These results prompted us to further screen the reaction conditions. In the next step of synthetic work, we considered the formation of product 3a under reflux conditions ( Table 1, entry 12 ). We found that reflux conditions prevent product 3a formation ( please refer to Scheme 1 ). Hence, the best results for synthesizing product 3a were obtained at 25 ºC under catalyst-free conditions and after 2 h of stirring ( Table 1, entry 11 ). The general procedure used for synthesizing product 3a was also employed for compound 4a , except using dimethylamine in place of methylamine ( Table 1, entry 13 ). To our surprise, products 3a and 4a were easily converted to dispirocyclopentanebisoxindoles ( 5a-5d ) under basic conditions ( Table 1, entries 15-25 ). This conversion proceeded well in the presence of different bases such as LDA, KOH, NaOH, and K 2 CO 3 via one-pot operation after 30-90 min of stirring. In contrast, Et 3 N converted products 3a and 4a to isatin chalcone and was not able to convert 3a and 4a to dispirocyclopentanebisoxindole products ( Table 1, entry 26 ). In the next step of synthetic work, with the optimal reaction conditions in hand, the generality for substrates was also studied ( Table 2 ). Most functional groups were tolerable and the reaction was carried out successfully with various substituents on the nitrogen and the aromatic ring of the isatin. Moreover, the reaction gave satisfactory answers with different aromatic and aliphatic amines. 1 H and 13 C NMR, FT-IR, and elemental analysis determined the structure of the final products. Compound 3c and 5g were also crystallized from EtOAc by slow evaporation at room temperature and the structure was confirmed by X -ray crystallographic analysis ( Figure 1 ). To understand the sequence of steps of the reaction, we proposed a plausible mechanism as illustrated in Scheme 2. In the beginning, isatin derivatives reacted with phosphonium ylide to form isatin chalcone A . In addition, carbamodithioic acid B could be resulted from the addition of the amine to carbon disulfide. Subsequent attack of the carbamodithioic acid B on isatin chalcone A lead to the formation of intermediate C . Finally, the intramolecular attack on the carbonyl yields the final thioxothiazolidin-indolin-2-one products. Following, in basic media, the thioxothiazolidin-indolin-2-one could be converted to dispirocyclopentanebisoxindoles via sequential condensation, Michael addition, and intramolecular cyclization reaction. Scheme 2. Proposed mechanism for the formation of final products The products 3a-3w and 5a-5g were racemic mixtures (0 % ee value) owing to the lack of chiral inducing agents. To obtain the related enantiomeric products in unequal amounts, we used the (-)-quinine ( 6 , 30 mol%) as a chiral catalyst. Unfortunately, all our attempts to induce enantioselectivity and obtain the asymmetric version of the final products failed (Scheme 3). To show that these synthetic procedures are certainly worthwhile, we eventually tested the gram scale synthesis of products 3a and 5a (Scheme 4). For this reason, to a solution of N- allyl isatin ( 1a , 6.0 mmol, 1.12 g) in MeOH, phosphonium ylide ( 2, 6.0 mmol, 1.53 g) was added and stirred at room temperature for 30 min to afford the corresponding isatin chalcone. In the next step, carbon disulfide (6.0 mmol, 0.36 mL) and methylamine (6.0 mmol, 0.52 mL) were added to the reaction mixture and stirred for more 1.5 h to form product 3a . Upon completion of the reaction, the reaction color changes from red to pale yellow. In this stage, we added KOH (0.8 equiv.) to form dispirocyclopentanebisoxindole ( 5a ). After completion of the reaction, the organic products were simply filtered off and the precipitate was washed with EtOH. We were delighted to obtain the products 3a and 5a in 71 and 76 % yield, respectively. Scheme 3. Study on catalytic asymmetric induction Scheme 4. Scale-up Reaction 3. Conclusion In this publication, we reported an efficient and facile synthesis of thioxothiazolidin-indolin-2-one and oxoindolin-carbamodihioate hybrids from isatin chalcones and achieved success in their base-catalyzed conversion into dispirocyclopentanebisoxindoles. The procedure exhibited great efficiency in providing final products with decent yields from accessible starting materials and displaying excellent regio- and diastereoselectivity. Short reaction time, mild reaction conditions, satisfying the green chemistry standards, easy reaction workup, a favorable response to gram-scale synthesis, excellent regio- and diastereoselectivity, readily accessible source of starting materials, and one-pot synthetic operation are some advantages of this work. 4. Experimental Section 4.1 . General Remarks. All solvents and starting materials were purchased from Merck and Sigma-Aldrich used without any additional purification. Analytical TLC was carried out using Merck 0.2 mm silica gel 60 F-254 Al-plates. 1 H NMR and 13 C NMR spectra were recorded on a Bruker Avance DRX-500 machine using DMSO- d 6 as solvent and TMS as an internal standard at room temperature (DMSO- d 6 1 H NMR: δ (ppm) =2.50 ppm; 13 C NMR: δ (ppm) =39.9 ppm; CDCl 3 1 HNMR: δ (ppm) = 7.26 and 13 C-NMR: δ (ppm) = 77.00 ppm). Chemical shifts were reported in ppm scale. FT-IR spectra of samples were obtained on ABB Bomem MB100 spectrometer with potassium bromide (KBr) pellets. Melting points were determined using an Electrothermal 9100 apparatus and are uncorrected. Elemental analysis was done by LECO Truspec. 4.2. Experimental procedure for the synthesis of compounds 3 (3a-3w), 4 (4a-4d), and 5 (5a-5g). To a solution of isatin derivatives ( 1a-1w , 0.3mmol) in alcoholic solvents (2.0 mL), phosphonium ylide ( 2, 0.3 mmol) was added and stirred at room temperature for 30 min to afford the corresponding isatin chalcone. Upon completion of the reaction, the reaction color changes from orange to red. In the next step, carbon disulfide (0.3 mmol) and primary (1°) amines (0.3 mmol) were added to the reaction mixture and stirred for more 1.5 h to form products 3a-3w (the general procedure used for synthesizing the products 3a-3w was also employed for compounds 4a-4d ,except using secondary (2°) amines in place of primary (1°) amines). Upon completion of the reaction, the reaction color changes from red to pale yellow. In this stage, if we added KOH (15 mg, 0.8 equiv.) to the reaction mixture, products 3 or 4 easily converted to dispirocyclopentane- bisoxindoles ( 5a-5g ) after 30-90 min of stirring (first, the reaction color changes from pale yellow to red, and then from red to white). After completion of the reaction, the organic products were simply filtered off and the precipitate was washed with EtOH. The pure products were dried in air and directly characterized by 1 H NMR, 13 C NMR, elemental and FT-IR analysis. In addition, the structure of compound 3c was confirmed by X -ray crystallographic analysis. 1-allyl-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3a) white solid; yield (96 mg, 81 %); m.p. 178-180 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.09 (3H, s), 4.35 (1H, d.d., J = 5.0 Hz), 4.44 (1H, d, J = 5.0 Hz), 4.46 (1H, d, J = 5.0 Hz), 4.53 (1H, d.d, J = 5.0 Hz), 5.33 (2H, quintet, J = 15.0 Hz), 5.87 (1H, m), 6.93 (1H, d, J = 10.0 Hz), 7.08 (2H, t, J = 5.0 Hz), 7.31 -7.59 (6H, m), 8.15 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 32.7, 43.2, 46.9, 56.8, 100.2, 110.2, 118.6, 123.7, 123.8, 124.8, 125.4, 129.2, 129.3, 129.4, 130.2, 141.8, 143.5, 176.5, 191.4 ppm; IR (KBr) ν= 3300-3080, 1675, 1640, 1609 cm -1 ; Anal. Calcd. for C 21 H 20 N 2 O 2 S 2 : C, 63.61; H, 5.08; N, 7.06; Found: C, 63.45; H, 5.16; N, 6.75 %. 1-benzyl-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3b) white solid; yield (112 mg, 84 %); m.p. 160-162 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.12 (3H, s), 4.46 (1H, d, J = 5.0 Hz), 4.52 (1H, d, J = 5.0 Hz), 4.79 (1H, d, J = 10.0 Hz), 5.23 (1H, d, J = 10.0 Hz), 6.81 (1H, d, J = 10.0 Hz), 7.05 (2H, t, J = 5.0 Hz), 7.23 -7.62 (11H, m), 8.19 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 32.7, 44.8, 47.0, 56.9, 100.2, 110.4, 123.7, 123.8, 124.7, 125.4, 127.6, 128.1, 129.1, 129.2, 129.3, 129.4, 134.5, 141.8, 143.5, 176.9, 191.4 ppm; IR (KBr) ν= 3300-3161, 1675, 1614 cm -1 ; Anal. Calcd. for C 25 H 22 N 2 O 2 S 2 : C, 67.24; H, 4.97; N, 6.27; Found: C, 67.01; H, 5.11; N, 6.08 %. 3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3c) white solid; yield (102 mg, 86 %); m.p. 172-174 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.04 (3H, t, J = 10.0 Hz), 1.78 (2H, m), 3.09 (3H, s), 3.69 (1H, m), 3.86 (1H, m), 4.42 (1H, d, J = 5.0 Hz), 4.43 (1H, d, J = 5.0 Hz), 6.96 (1H, d, J = 10.0 Hz), 7.08 (2H, t, J = 5.0 Hz), 7.34 -7.60 (6H, m), 8.27 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 11.6, 20.8, 32.7, 42.6, 46.8, 56.8, 100.2, 109.6, 123.6, 123.8, 124.7, 124.8, 125.6, 129.2, 129.4, 141.9, 143.9, 176.7, 191.4 ppm; IR (KBr) ν= 3300-3050, 1670, 1609 cm -1 ; Anal. Calcd. for C 21 H 22 N 2 O 2 S 2 : C, 63.29; H, 5.56; N, 7.03; Found: C, 62.97; H, 5.68; N, 6.87 % 5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3d) white solid; yield (100 mg, 77 %); m.p. 150-152 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.03 (3H, t, J = 5.0 Hz), 1.76 (2H, m), 3.08 (3H, s), 3.66 (1H, m), 3.84 (1H, m), 4.37 (1H, d, J = 5.0 Hz), 4.42 (1H, d, J = 5.0 Hz), 6.88 (1H, d, J = 10.0 Hz), 7.08 (1H, s), 7.33 -7.57 (6H, m), 8.06 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 11.5, 20.8, 32.7, 42.8, 46.9, 56.6, 100.1, 100.2, 110.5, 124.3, 124.7, 127.2, 129.3, 129.4, 129.5, 141.6, 142.5, 176.2, 191.1 ppm; IR (KBr) ν = 3300-3056, 1675, 1609 cm -1 ; Anal. Calcd. for C 21 H 21 ClN 2 O 2 S 2 : C, 58.25; H, 4.89; N, 6.47; Found: C, 58.01; H, 5.04; N, 6.21 % 1-allyl-5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3e) white solid; yield (107 mg, 83 %); m.p. 154-156 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.08 (3H, s), 4.32 (1H, d.d, J = 5.0 Hz), 4.39 (1H, d, J = 5.0 Hz), 4.47 (1H, d, J = 5.0 Hz), 4.54 (1H, d.d, J = 5.0 Hz), 5.33 (2H, quintet, J = 15.0 Hz), 5.84 (1H, m), 6.86 (1H, d, J = 10.0 Hz), 7.09 (1H, s), 7.31 -7.58 (6H, m), 7.95 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 32.8, 43.3, 46.9, 56.6, 100.2, 111.2, 118.9, 124.3, 124.7, 127.1, 129.3, 129.4, 129.9, 141.5, 156.7, 176.5, 191.0 ppm; IR (KBr) ν= 3300-3086, 1672, 1643, 1612 cm -1 ; Anal. Calcd. for C 21 H 19 ClN 2 O 2 S 2 : C, 58.53; H, 4.44; N, 6.50; Found: C, 58.22; H, 4.51; N, 6.35 %. 1-benzyl-5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3f) white solid; yield (114 mg, 79 %); m.p. 128-130 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.12 (3H, s), 4.41 (1H, d, J = 5.0 Hz), 4.54 (1H, d, J = 5.0 Hz), 4.75 (1H, d, J = 10.0 Hz), 5.23 (1H, d, J = 10.0 Hz), 6.73 (1H, d, J = 10.0 Hz), 7.03 (1H, s), 7.21 -7.60(11H, m), 7.99 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 32.8, 44.9, 47.1, 56.7, 100.2, 111.3, 124.2, 124.7, 127.1, 127.6, 128.3, 129.2, 129.3, 129.4, 129.5, 129.5, 134.0, 141.5, 142.0, 176.5, 191.0 ppm; IR (KBr) ν= 3350-3100, 1678, 1615 cm -1 ; Anal. Calcd. for C 25 H 21 ClN 2 O 2 S 2 : C, 62.42; H, 4.40; N, 5.82; Found: C, 62.15; H, 4.53; N, 5.65%. 3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3g) white solid; yield (101 mg, 91 %); m.p. 170-172 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.09 (3H, s), 3.33 (3H, s), 4.43 (1H, d, J = 5.0 Hz), 4.45 (1H, d, J = 5.0 Hz), 6.94 (1H, d, J = 10.0 Hz), 7.09 (2H, t, J = 5.0 Hz), 7.36 -7.59 (6H, m), 8.26 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 27.0, 32.8, 46.9, 56.7, 100.2, 109.3, 123.6, 123.9, 124.7, 125.3, 129.2, 129.3, 129.5, 142.0, 144.3, 176.6, 191.5 ppm; IR (KBr) ν= 3400-3150, 1676, 1604 cm -1 ; Anal. Calcd. for C 19 H 18 N 2 O 2 S 2 : C, 61.60; H, 4.90; N, 7.56; Found: C, 61.35; H, 4.96; N, 7.41 % 3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3h) white solid; yield (93 mg, 87 %); m.p. 164-166 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.09 (3H, s), 4.44 (1H, d, J = 5.0 Hz), 4.46 (1H, d, J = 5.0 Hz), 6.98 (1H, d, J = 10.0 Hz), 7.07 (2H, t, J = 5.0 Hz), 7.32 -7.59 (6H, m), 7.88 (1H, s), 8.10 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 32.8, 47.3, 56.7, 100.2, 109.6, 123.8, 124.0, 124.7, 125.9, 129.3, 129.4, 129.5, 141.2, 141.7, 178.4, 191.7 ppm; IR (KBr) ν= 3350, 3300-3150, 1673, 1610 cm -1 ; Anal. Calcd. for C 18 H 16 N 2 O 2 S 2 : C, 60.65; H, 4.52; N, 7.86; Found: C, 60.53; H, 4.60; N, 7.75 % 3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-isopropylindolin-2-one (3i) white solid; yield (110 mg, 92%); m.p. 180-182 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.56 (6H, d, J = 5.0 Hz), 3.09 (3H, s), 4.36 (1H, d, J = 5.0 Hz), 4.38 (1H, d, J = 5.0 Hz), 4.63 (1H, septet, J = 5.0 Hz), 7.06 (2H, t, J = 5.0 Hz), 7.10 (1H, d, , J = 10.0 Hz), 7.32 -7.58 (6H, m), 8.32 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 19.3, 19.6, 32.7, 45.4, 46.7, 57.4, 100.2, 110.8, 123.3, 123.9, 124.8, 125.9, 129.3, 129.3, 141.8, 143.2, 176.5, 191.5 ppm; Anal. Calcd. for C 21 H 22 N 2 O 2 S 2 : C, 63.29; H, 5.56; N, 7.03; Found: C, 63.13; H, 5.64; N, 6.85 % Ethyl-2-(3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-2-oxoindolin-1-yl)acetate (3j) white solid; yield (126 mg, 95%); m.p. 142-144 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.31 (3H, t, J = 5.0 Hz), 3.08 (3H, s), 4.28 (2H, q, J = 5.0 Hz), 4.42 (1H, d, J = 15.0 Hz), 4.47 (1H, d, J = 5.0 Hz), 4.53 (1H, d, J = 5.0 Hz), 4.68 (1H, d, J = 15.0 Hz), 6.83 (1H, d, J = 10.0 Hz), 7.12 (2H, t, J = 5.0 Hz), 7.30 -7.61 (6H, m), 7.88 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 14.3, 32.8, 42.1, 46.8, 56.6, 62.3, 100.2, 109.3, 123.9, 124.2, 124.8, 125.1, 129.3, 129.3, 129.5, 141.8, 143.0, 166.8, 176.9, 191.6 ppm; Anal. Calcd. for C 22 H 22 N 2 O 4 S 2 : C, 59.71; H, 5.01; N, 6.33; Found: C, 59.63; H, 5.11; N, 6.21 % 3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-(naphthalen-1-ylmethyl) indolin-2-one (3k) white solid; yield (119 mg, 80%); m.p. 176-178 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.11 (3H, s), 4.52 (1H, d, J = 5.0 Hz), 4.61 (1H, d, J = 5.0 Hz), 5.44 (1H, d, J = 10.0 Hz), 5.57 (1H, d, J = 10.0 Hz), 6.74(1H, d, J = 10.0 Hz), 7.05-7.21 (3H,m), 7.44-7.69 (9H, m), 7.84 (1H, d, J = 10.0 Hz), 7.94 (1H, d, J = 10.0 Hz), 8.11 (1H, d, J = 10.0 Hz) 8.22 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 32.8, 42.7, 47.2, 56.9, 100.3, 110.6, 122.6, 123.7, 124.0, 124.7, 124.8, 125.5, 126.0, 126.1, 126.9, 128.6, 129.1, 129.2, 129.3, 129.4, 129.5, 130.9, 133.9, 141.8, 143.8, 177.1, 191.3 ppm; Anal. Calcd. for C 29 H 24 N 2 O 2 S 2 : C, 70.13; H, 4.87; N, 5.64; Found: C, 69.97; H, 5.04; N, 5.49% 1-benzyl-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3l) white solid; yield (114 mg, 83 %); m.p. 152-154 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.29 (3H, t, J = 5.0 Hz), 3.35 (1H, q, J = 10.0 Hz), 3.94 (1H, q, J = 5.0 Hz), 4.42 (1H, d, J = 5.0 Hz), 4.52 (1H, d, J = 5.0 Hz), 4.79 (1H, d, J = 15.0 Hz), 5.25 (1H, d, J = 15.0 Hz), 6.82 (1H, d, J = 10.0 Hz), 7.06 (2H, t, J = 5.0 Hz), 7.18 -7.65 (11H, m), 8.26 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 13.4, 42.3, 44.7, 47.1, 57.0, 100.9, 110.3, 123.7, 123.8, 124.8, 125.5, 127.6, 128.1, 129.1, 129.2, 129.3, 129.4, 134.5, 142.6, 143.6, 177.0, 190.8 ppm; Anal. Calcd. for C 26 H 24 N 2 O 2 S 2 : C, 67.80; H, 5.25; N, 6.08; Found: C, 67.61; H, 5.37; N, 5.93 %. 1-allyl-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3m) white solid; yield (93 mg, 76 %); m.p. 136-138 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.26 (3H, t, J = 10.0 Hz), 3.32 (1H, q, J = 10.0 Hz), 3.90 (1H, q, J = 10.0 Hz), 4.37 (1H, d.d, J = 5.0 Hz), 4.41 (1H, d, J = 5.0 Hz), 4.46 (1H, d.d, J = 5.0 Hz), 4.51 (1H, d, J = 5.0 Hz), 5.33 (2H, quintet, J = 15.0 Hz), 5.85 (1H, m), 6.92 (1H, d, J = 10.0 Hz), 7.09 (2H, t, J = 5.0 Hz), 7.34 -7.62 (6H, m), 8.20 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 13.4, 42.3, 43.1, 47.0, 56.9, 100.9, 110.1, 118.5, 123.7, 123.8, 124.8, 125.4, 129.1, 129.3, 129.4, 130.2, 142.6, 157.5, 176.5, 190.8 ppm; Anal. Calcd. for C 22 H 22 N 2 O 2 S 2 : C, 64.36; H, 5.40; N, 6.82; Found: C, 64.27; H, 5.51; N, 6.68 %. 3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3n) white solid; yield (91 mg, 74 %); m.p. 140-142 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.04 (3H, t, J = 10.0 Hz), 1.26 (3H, t, J = 10.0 Hz), 1.79 (2H, m), 3.32 (1H, m), 3.72 (1H, m), 3.89 (2H, m), 4.39 (1H, d, J = 5.0 Hz), 4.41 (1H, d, J = 5.0 Hz), 6.95 (1H, d, J = 10.0 Hz), 7.07 (2H, t, J = 5.0 Hz), 7.26 -7.62 (6H, m), 8.34 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 11.6, 13.4, 20.8, 40.2, 42.6, 47.0, 56.9, 100.9, 109.6, 123.6, 123.8, 124.8, 125.6, 129.1, 129.2, 129.4, 142.7, 144.0, 176.7, 190.9 ppm; Anal. Calcd. for C 22 H 24 N 2 O 2 S 2 : C, 64.15; H, 5.86; N, 6.79; Found: C, 63.81; H, 5.92; N, 6.58 % 5-chloro-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3o) white solid; yield (114 mg, 85 %); m.p. 134-136 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.03 (3H, t, J = 10.0 Hz), 1.25 (3H, t, J = 10.0 Hz), 1.78 (2H, m), 3.30 (1H, t, J = 5.0 Hz), 3.68 (1H, t, J = 5.0 Hz), 3.88 (2H, m), 4.32 (1H, , d, J = 5.0 Hz), 4.42 (1H, d, J = 5.0 Hz), 6.88 (1H, d, J = 10.0 Hz), 7.07 (1H, s), 7.32 -7.60 (6H, m), 8.12 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 11.5, 13.3, 20.8, 42.3, 42.7, 47.0, 56.7, 100.9, 110.5, 121.4, 124.3, 124.7, 129.2, 129.4, 142.4, 156.2, 176.3, 190.5 ppm; Anal. Calcd. for C 22 H 23 ClN 2 O 2 S 2 : C, 59.11; H, 5.19; N, 6.27; Found: C, 58.93; H, 5.24; N, 6.12 % ethyl-2-(3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-2-oxoindolin-1-yl)acetate (3p) white solid; yield (103 mg, 75 %); m.p. 138-140 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.26 (3H, t, J = 5.0 Hz), 1.32 (3H, t, J = 5.0 Hz), 3.30 (1H, q, J = 5.0 Hz), 3.91 (1H, q, J = 5.0 Hz), 4.28 (2H, q, J = 5.0 Hz), 4.40 (1H, d, J = 15.0 Hz), 4.44 (1H, d, J = 5.0 Hz), 4.53 (1H, d, J = 5.0 Hz), 4.73 (1H, d, J = 15.0 Hz), 6.83 (1H, d, J = 10.0 Hz), 7.10 (2H, t, J = 5.0 Hz), 7.33 -7.61 (6H, m), 7.91 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 13.4, 14.3, 42.1, 42.3, 47.0, 56.6, 62.3, 100.9, 109.3, 123.9, 124.1, 124.8, 125.1, 129.2, 129.3, 129.5, 142.6, 143.1, 166.9, 176.9, 191.0 ppm; Anal. Calcd. for C 23 H 24 N 2 O 4 S 2 : C, 60.51; H, 5.30; N, 6.14; Found: C, 60.38; H, 5.42; N, 5.97 % 1-benzyl-5-chloro-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3q) white solid; yield (121 mg, 82 %); m.p. 198-200 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.57 (3H, t, J = 5.0 Hz), 3.53 (2H, q, J = 10.0 Hz), 3.94 (1H, d, J = 5.0 Hz), 4.16 (1H, d, J = 5.0 Hz), 4.99 (2H, s), 6.66 (1H, d, J = 10.0 Hz), 7.14 (1H, d, J = 5.0 Hz), 7.27 -7.63 (10H, m), 8.02 (1H,s) 8.04 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 39.9, 41.3, 44.2, 110.0, 125.0, 127.3, 127.8, 127.9, 128.0, 128.3, 128.3, 128.8, 129.0, 130.8, 133.7, 135.5, 142.1, 177.4, 196.5 ppm; Anal. Calcd. for C 26 H 23 ClN 2 O 2 S 2 : C, 63.08; H, 4.68; N, 5.66; Found: C, 62.81; H, 4.76; N, 5.41 % 3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3r) white solid; yield (106 mg, 92 %); m.p. 140-142 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.27 (3H, t, J = 5.0 Hz), 3.30 (1H, m), 3.34 (3H, s), 3.90 (1H, m), 4.42 (1H, d, J = 5.0 Hz), 4.43 (1H, d, J = 5.0 Hz), 6.94 (1H, d, J = 10.0 Hz), 7.09 (2H, m), 7.38 -7.62 (6H, m), 8.30 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 13.4, 27.0, 42.3, 47.1, 56.7, 101.0, 109.3, 123.6, 123.8, 124.8, 125.3, 129.1, 129.3, 129.5, 142.8, 144.3, 176.7, 190.9 ppm; Anal. Calcd. for C 20 H 20 N 2 O 2 S 2 : C, 62.47; H, 5.24; N, 7.29; Found: C, 62.21; H, 5.33; N, 7.10 % 3-(-3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3s) white solid; yield (125 mg, 88 %); m.p. 130-132 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 1.07 (3H, t, J = 10.0 Hz), 1.81 (2H, m), 3.70 (1H, t, J = 10.0 Hz), 3.87(1H, t, J = 10.0 Hz), 4.36 (1H, d, J = 5.0 Hz), 4.48 (1H, d, J = 5.0 Hz), 4.52 (1H, d, J = 10.0 Hz), 5.12 (1H, d, J = 10.0 Hz), 6.95 (1H, d, J = 10.0 Hz), 7.07 (2H, t, J = 5.0 Hz), 7.20 -7.59 (11H, m), 8.25 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 11.7, 20.9, 42.6, 46.7, 50.2, 57.0, 101.0, 109.6, 123.6, 123.8, 125.0, 125.5, 127.0, 128.0, 128.4, 129.0, 129.2, 129.5, 136.7, 142.6, 143.9, 176.5, 193.0 ppm; Anal. Calcd. for C 27 H 26 N 2 O 2 S 2 : C, 68.33; H, 5.52; N, 5.90; Found: C, 68.10; H, 5.61; N, 5.76 %. 3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3t) white solid; yield (122 mg, 91 %); m.p. 140-142 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.34 (3H, s), 4.38 (1H, d, , J = 5.0 Hz), 4.48 (1H, d, J = 10.0 Hz), 4.51 (1H, d, J = 5.0 Hz), 5.14 (1H, d, J = 10.0 Hz), 6.93 (1H, d, J = 10.0 Hz), 7.09 (2H, t, J = 5.0 Hz), 7.21-7.59 (11H, m), 8.17 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 27.1, 46.7, 50.3, 56.8, 101.1, 109.3, 123.7, 123.8, 125.0, 127.0, 128.0, 128.3, 129.0, 129.2, 129.6, 132.0, 136.6, 142.7, 144.3, 176.5, 193.1 ppm; Anal. Calcd. for C 25 H 22 N 2 O 2 S 2 : C, 67.24; H, 4.97; N, 6.27; Found: C, 66.98; H, 5.11; N, 6.03 %. 1-allyl-3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3u) white solid; yield (123 mg, 87 %); m.p. 132-134°C; 1 H NMR (500 MHz, CDCl 3 ) δ 4.41 (2H, d, J = 5.0 Hz), 4.48 (1H, d.d, J = 5.0 Hz), 4.50 (1H, d, J = 5.0 Hz), 4.52 (1H, d.d, J = 5.0 Hz), 5.14 (1H, d, J = 10.0 Hz), 5.35 (2H, quintet, J = 10.0 Hz), 5.90 (1H, m), 6.93 (1H, d, J = 5.0 Hz), 7.08 (2H, t, J = 5.0 Hz), 7.20 -7.60 (11H, m), 8.09 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 43.1, 46.7, 50.2, 57.0, 101.0, 110.2, 118.6, 123.7, 125.0, 125.3, 127.0, 128.0 , 128.4, 129.0, 129.2, 129.4, 130.4, 136.6, 142.5, 143.5, 176.3, 193.0 ppm; Anal. Calcd. for C 27 H 24 N 2 O 2 S 2 : C, 68.62; H, 5.12; N, 5.93; Found: C, 68.43; H, 5.26; N, 5.78 %. 1-benzyl-3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3v) white solid; yield (124 mg, 79 %); m.p. 154-156 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 4.46 (1H, d, J = 5.0 Hz), 4.49 (1H, d, J = 5.0 Hz), 4.51 (1H, d, J = 5.0 Hz), 4.80 (1H, d, J = 10.0 Hz), 5.20 (2H, d, J = 10.0 Hz), 6.82 (1H, d, J = 10.0 Hz), 7.05 (2H, t, J = 5.0 Hz), 7.19 -7.62 (16H, m), 8.10 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 44.7, 46.8, 50.3, 57.0, 101.1, 110.2, 123.7, 123.8, 124.9, 125.4, 127.0, 127.6, 128.0, 128.1, 128.5, 129.0, 129.2, 129.2, 129.4, 134.7, 136.7, 142.6, 143.5, 176.7, 193.0 ppm; Anal. Calcd. for C 31 H 26 N 2 O 2 S 2 : C, 71.24; H, 5.01; N, 5.36; Found: C, 71.02; H, 5.12; N, 5.10 %. 3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-(naphthalen-1-ylmethyl) indolin-2-one (3w) white solid; yield (132 mg, 77%); m.p. 140-142 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 4.49 (1H, d, J = 5.0 Hz), 4.52 (1H, d, J = 5.0 Hz), 4.56 (1H, d, J = 10.0 Hz), 5.19 (1H, d, J = 10.0 Hz), 5.43 (1H, d, J = 10.0 Hz), 5.58 (1H, d, J = 10.0 Hz), 6.75(1H, d, J = 10.0 Hz), 7.05-7.69 (17H, m), 7.86 (1H, d, J = 10.0 Hz), 7.95 (1H, d, J = 10.0 Hz), 8.14 (1H, d, J = 10.0 Hz) 8.16 (1H, s) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 42.8, 47.0, 50.3, 56.9, 100.0, 101.1, 110.6, 122.7, 123.7, 123.9, 124.9, 125.0, 125.9, 126.2, 127.0, 127.0, 128.0, 128.3, 128.7, 129.1, 129.2, 129.3, 129.3, 129.5, 130.9, 133.9, 136.6, 142.6, 143.8, 176.9, 192.9 pm; Anal. Calcd. for C 35 H 28 N 2 O 2 S 2 : C, 73.40; H, 4.93; N, 4.89; Found: C, 73.27; H, 5.09; N, 4.71 % 1-(1-allyl-2-oxoindolin-3-yl)-2-oxo-2-phenylethyldimethyl- carbamodithioate (4a) white solid; yield (102 mg, 83 %); m.p. 114-116 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.38 (3H, s), 3.62 (3H, s), 3.92 (1H, d, J = 5.0 Hz), 4.47 (2H, d.d, J = 5.0 Hz), 5.35 (2H, d.d, J = 5.0 Hz), 5.97 (1H, quintet, J = 5.0 Hz), 6.84 (2H, d, J = 5.0 Hz), 7.01 (1H, d, J = 5.0 Hz), 7.25 (1H, d, J = 5.0 Hz), 7.43 -7.58 (4H, m), 8.02 (2H, d , J = 10.0 Hz) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 35.2, 42.5, 46.2, 57.5, 109.2, 117.8, 122.9, 126.6, 127.8, 128.5, 128.7, 128.9, 131.2, 131.7, 132.6, 133.9, 136.4, 137.7, 176.1, 191.3, 194.1 ppm; Anal. Calcd. for C 22 H 22 N 2 O 2 S 2 : C, 64.36; H, 5.40; N, 6.82; Found: C, 64.24; H, 5.48; N, 6.67 %. 1-(1-benzyl-2-oxoindolin-3-yl)-2-oxo-2-phenylethyldimethyl- carbamodithioate (4b) white solid; yield (102 mg, 74 %); m.p. 140-142 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.38 (3H, s), 3.63 (3H, s), 4.01 (1H, d, J = 5.0 Hz), 5.05 (2H, d, J = 10.0 Hz), 6.71 (1H, d, J = 5.0 Hz), 6.88 (1H, d, J = 5.0 Hz), 6.98 (1H, t, J = 5.0 Hz), 7.16 (1H, t, J = 5.0 Hz), 7.34 -7.59 (9H, m), 8.05 (2H, d , J = 10.0 Hz) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 41.7, 44.1, 46.3, 46.5, 57.5, 94.4, 109.1, 122.4, 123.9, 126.5, 127.5, 127.6, 128.5, 128.7, 129.0, 133.6, 134.9, 136.2, 143.6, 176.3, 194.2, 194.2 ppm; Anal. Calcd. for C 26 H 24 N 2 O 2 S 2 : C, 67.80; H, 5.25; N, 6.08; Found: C, 67.57; H, 5.37; N, 5.92%. 1-(1-allyl-5-chloro-2-oxoindolin-3-yl)-2-oxo-2-phenylethyl dimethylcarbamodithioate (4c) white solid; yield (108 mg, 81 %); m.p. 110-112 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.39 (3H, s), 3.64 (3H, s), 3.90 (1H, d, J = 5.0 Hz), 4.45 (2H, d.d, J = 5.0 Hz), 5.34 (2H, d.d, J = 5.0 Hz), 5.95 (1H, quintet, J = 5.0 Hz), 6.79 (2H, d, J = 5.0 Hz), 7.20 (1H,d, J = 5.0 Hz), 7.45 -7.60 (4H, m), 7.97 (2H, d , J = 10.0 Hz) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 41.6, 42.6, 46.2, 46.6, 57.5, 100.0, 109.9, 117.8, 124.2, 127.9, 128.4, 128.9, 129.3, 131.3, 132.2, 133.8, 134.7, 164.6, 184.5, 193.9 ppm; Anal. Calcd. for C 22 H 21 ClN 2 O 2 S 2 : C, 59.38; H, 4.76; N, 6.30; Found: C, 59.22; H, 4.84; N, 6.21 %. 1-(1-benzyl-5-chloro-2-oxoindolin-3-yl)-2-oxo-2-phenylethyl dimethylcarbamodithioate (4d) white solid; yield (119 mg, 80 %); m.p. 132-134 °C; 1 H NMR (500 MHz, CDCl 3 ) δ 3.39 (3H, s), 3.99 (3H, s), 3.99 (1H, d, J = 5.0 Hz), 5.03 (2H, d, J = 10.0 Hz), 6.61 (1H, d, J = 5.0 Hz), 6.85 (1H, d, J = 5.0 Hz), 7.12(1H, d, J = 5.0 Hz), 7.35 -7.60 (9H, m), 8.01 (2H, d , J = 10.0 Hz) ppm; 13 C NMR (176 MHz, CDCl 3 ) δ 41.7, 44.2, 46.4, 46.7, 57.5, 110.0, 124.3, 127.5, 127.7, 128.4, 128.8, 128.8, 129.0, 133.8, 134.6, 135.8, 142.2, 176.0, 193.9, 194.0 ppm; Anal. Calcd. for C 26 H 23 ClN 2 O 2 S 2 : C, 63.08; H, 4.68; N, 5.66; Found: C, 62.81; H, 4.81; N, 5.49 %. 1,1''-diallyl-2'-benzoyl-4'-hydroxy-5'-methoxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5a) white solid; yield (79 mg, 86 %); m.p. 258-260 °C; 1 H NMR (500 MHz, DMSO-d 6 ) δ 2.95 (3H, s), 3.93 (2H, d.d, J = 15.0 Hz), 4.21 (1H, d, J = 15.0 Hz), 4.53 (2H, d.d, J = 15.0 Hz), 4.80 (1H, d, J = 15.0 Hz), 5.14 (1H, quintet, J = 10.0 Hz), 5.21 (2H, t, J = 15.0 Hz), 5.27 (1H, s ), 5.77 (1H, quintet, J = 10.0 Hz), 5.96 (1H, s ), 6.57 (1H, d, J = 5.0 Hz ), 6.63 (1H, d, J = 5.0 Hz ), 6.68 (1H, s), 6.98 -7.23 (13H, m), 7.374 (1H, t, J = 5.0 Hz ), 7.86 (1H, d, J = 5.0 Hz), 8.06 (1H, d, J = 5.0 Hz) ppm; 13 C NMR (176 MHz, DMSO-d 6 ) δ 41.9, 43.1, 58.3, 60.0, 60.7, 61.6, 84.5, 89.3, 100.0, 108.8, 109.4, 116.9, 118.4, 122.0, 123.9, 125.0, 125.9, 126.2, 126.6, 127.3, 127.6, 127.9, 129.1, 130.6, 131.6, 131.9, 133.3, 136.8, 137.6, 142.5, 143.8, 176.3, 179.3, 196.6 ppm; Anal. Calcd. for C 39 H 34 N 2 O 5 : C, 76.70; H, 5.61; N, 4.59; Found: C, 76.51; H, 5.76; N, 4.34 %; 2'-benzoyl-4'-hydroxy-1,1''-dimethyl-5'-(octyloxy)-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5b) white solid; yield (88 mg, 89 %); m.p. 222-224 °C; 1 H NMR (500 MHz, DMSO-d6) δ 0.79-1.19 (15H, m), 2.79 (3H,s), 2.85 (1H, t, J = 10.0 Hz), 3.08 (3H,s), 3.17 (1H, t, J = 10.0 Hz), 5.22 (1H, s), 5.99 (1H, s), 6.56 (1H, d, J = 5.0 Hz), 6.75 (2H, t, J = 5.0 Hz), 6.97 -7.49 (14H, m), 7.82 (1H, d, J = 5.0 Hz), 8.09 (1H, d, J = 5.0 Hz) ppm; 13 C NMR (176 MHz, DMSO-d6) δ 14.4, 22.5, 25.8, 26.2, 27.1, 28.9, 29.0, 29.6, 31.6, 58.5, 61.6, 64.6, 84.6, 87.5, 108.0, 108.8, 112.7, 122.0, 123.8, 125.7, 126.1, 126.4, 126.7, 127.2, 127.3, 127.8, 128.4, 129.1, 130.6, 131.6, 133.2, 136.8, 137.5, 143.3, 144.5, 176.6, 179.7, 196.6 ppm; Anal. Calcd. for C 42 H 44 N 2 O 5 : C, 76.80; H, 6.75; N, 4.27; Found: C, 76.64; H, 6.83; N, 4.08 %. 1,1''-diallyl-2'-benzoyl-4'-hydroxy-4'-phenyl-5'-propoxydispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5c) white solid; yield (76 mg, 79 %); m.p. 166-168 °C; 1 H NMR (500 MHz, DMSO-d 6 ) δ 0.49 (3H, t, J = 10.0 Hz), 1.10 (2H, m), 2.88 (1H, q, J = 10.0 Hz), 3.13 (1H, q , J = 10.0 Hz), 3.97 (2H, d.d, J = 15.0 Hz ), 4.21 (1H, d, J = 15.0 Hz), 4.51 (2H, d.d, J = 15.0 Hz), 5.81 (1H, d, J = 15.0 Hz), 5.16 (1H, quintet, J = 10.0 Hz), 5.22 (1H, t, J = 15.0 Hz), 5.28 (1H, t, J = 10.0 Hz), 5.75 (1H, quintet, J = 10.0 Hz), 6.04 (1H, s ), 6.59 (1H, d, J = 5.0 Hz ), 6.64 (1H, d, J = 5.0 Hz ), 6.71 (1H, s), 6.98 -7.24 (13H, m), 7.37 (1H, t, J = 5.0 Hz ), 7.86 (1H, d, J = 5.0 Hz), 8.04 (1H, d, J = 5.0 Hz) ppm; 13 C NMR (176 MHz, DMSO-d 6 ) δ 10.7, 22.9, 41.9, 43.2, 58.4, 61.6, 64.5, 73.8, 84.5, 87.9, 100.0, 101.0, 108.8, 109.3, 116.9, 119.0, 122.0, 123.8, 125.9, 126.2, 126.7, 127.3, 127.5, 127.8, 128.7, 129.1, 130.5, 131.5, 131.9, 133.2, 136.8, 137.6, 142.6, 143.7, 176.3, 179.4, 196.6 ppm; Anal. Calcd. for C 41 H 38 N 2 O 5 : C, 77.09; H, 6.00; N, 4.39; Found: C, 76.89; H, 6.14; N, 4.21 % 4'-hydroxy-2'-methyl-4'-phenyl-5'-propoxy-1,1''-dipropyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5d) white solid; yield (72 mg, 75 %); m.p. 210-212 °C; 1 H NMR (500 MHz, DMSO-d 6 ) δ 0.49 (3H, t, J = 10.0 Hz), 0.55 (3H, t, J = 10.0 Hz), 0.93 (3H, t, J = 10.0 Hz), 1.00 (2H, m), 1.11 (2H, m), 1.47-1.66 (2H, m), 2.86-3.15 (2H, m ), 3.20-3.38 ( 2H, m), 3.50-3.77 (2H, m), 5.23 (1H, s), 6.03 (1H, s), 6.66 (1H, d, J = 10.0 Hz), 6.76 (1H, s), 6.79 (2H, d, J = 10.0 Hz), 6.96 (2H, d, J = 5.0 Hz), 7.02-7.19 (9H, m), 7.25 (1H, t, J = 10.0 Hz), 7.36 (1H, t, J = 10.0 Hz), 7.84 (1H, d, J = 5.0 Hz), 8.04 (1H, d, J = 5.0 Hz) ppm; 13 C NMR (176 MHz, DMSO-d 6 ) δ 10.7, 11.6, 11.9, 20.4, 21.0, 23.0, 41.3, 42.5, 58.4, 61.5, 64.2, 73.8, 84.6, 87.9, 100.0, 108.2, 109.0, 121.7, 123.6, 125.9, 126.1, 126.6, 127.2, 127.4, 128.6, 129.1, 130.7, 133.1, 136.9, 137.7, 143.1, 144.4, 176.4, 179.6, 196.6 ppm; Anal. Calcd. for C 41 H 42 N 2 O 5 : C, 76.61; H, 6.59; N, 4.36; Found: C, 76.43; H, 5.71; N, 4.19 2'-benzoyl-1,1''-di(but-2-en-1-yl)-4'-hydroxy-5'-methoxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5e) white solid; yield (79 mg, 83 %); m.p. 206-208 °C; 1 H NMR (500 MHz, DMSO-d 6 ) δ 1.41 (3H, d, J = 10.0 Hz ), 1.65 (3H, d, J = 10.0 Hz), 2.93 (3H, t, J = 10.0 Hz), 3.80 (1H, d, J = 10.0 Hz), 3.98 (1H, d, J = 10.0 Hz), 4.19 (1H, d, J = 10.0 Hz), 4.41 (1H, d, J = 10.0 Hz), 4.46 (1H, m), 5.93 (1H, m), 5.26 (1H, s ), 5.38 (1H, m), 5.72 (1H, m), 5.94 (1H, s ), 6.54-6.67 (3H, m), 6.92 -7.24 (13H, m), 7.36 (1H, t, J = 5.0 Hz ), 7.84 (1H, d, J = 5.0 Hz), 8.04 (1H, d, J = 5.0 Hz) ppm; 13 C NMR (176 MHz, DMSO-d 6 ) δ 13.4, 18.0, 36.6, 37.7, 41.0, 42.3, 58.2, 59.8, 61.4, 64.2, 84.5, 89.3, 108.7, 109.4, 121.9, 123.8, 124.2, 124.6, 125.9, 126.1, 126.7, 127.3, 127.5, 127.8, 128.6, 129.1, 129.8, 130.7 133.1, 136.8, 137.6, 142.5, 143.9, 176.1, 179.1, 196.5 ppm; Anal. Calcd. for C 41 H 38 N 2 O 5 : C, 77.09; H, 6.00; N, 4.39; Found: C, 76.88; H, 6.08; N, 4.19 % 2'-benzoyl-1,1''-di(but-2-en-1-yl)-5'-ethoxy-4'-hydroxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dionedione (5f) white solid; yield (79 mg, 81 %); m.p. 162-164 °C; 1 H NMR (500 MHz, DMSO-d 6 ) δ 0.72 (3H, t, J = 5.0 Hz ), 1.41 (3H, d, J = 10.0 Hz ), 1.64 (3H, d, J = 10.0 Hz), 2.95 (1H, q, J = 10.0 Hz), 3.23 (1H, q, J = 5.0 Hz), 3.80 (1H, d, J = 10.0 Hz), 3.95 (1H, d, J = 10.0 Hz), 4.19 (1H, d, J = 10.0 Hz), 4.42 (1H, d, J = 10.0 Hz), 4.4.67 (1H, m), 4.93 (1H, m), 5.26 (1H, s ), 5.39 (1H, m), 5.73 (1H, m), 6.03 (1H, s ), 6.56-6.69 (3H, m), 6.94 -7.24 (13H, m), 7.36 (1H, t, J = 5.0 Hz ), 7.84 (1H, d, J = 5.0 Hz), 8.02 (1H, d, J = 5.0 Hz) ppm; 13 C NMR (176 MHz, DMSO-d 6 ) δ 13.5, 15.6, 18.0, 36.6, 37.6, 41.0, 42.2, 58.4, 61.4, 64.2, 67.6, 84.6, 87.8, 108.7, 109.3, 121.9, 123.7, 124.3, 124.6, 125.9, 126.1, 126.5, 126.7, 127.3, 127.5, 127.8, 128.6, 129.1, 129.8, 130.7 133.1, 136.8, 137.6, 142.6, 143.9, 176.1, 179.2, 196.6 ppm; Anal. Calcd. for C 42 H 40 N 2 O 5 : C, 77.28; H, 6.18; N, 4.29; Found: C, 77.05; H, 6.32; N, 4.10% . 2'-benzoyl-5'-ethoxy-4'-hydroxy-4'-phenyl-1,1''-dimethyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5g) white solid; yield (70 mg, 85%); m.p. 266-268 °C; 1 H NMR (500 MHz, DMSO-d 6 ) δ 0.69 (3H, t, J = 10.0 Hz), 2.79 (3H, s), 2.96 (1H, q, J = 10.0 Hz), 3.11 (3H, s), 3.19 (1H, q, J= 10.0 Hz ), 5.23 (1H, s), 6.02 (1H, s), 6.58 (1H, d, J = 10.0 Hz), 6.75 (2H, d, J = 10.0 Hz), 6.90 -7.13 (10H, m), 7.18 (2H, t, J= 10.0 Hz), 7.26 (1H, t J= 10.0 Hz), 7.35 (1H, t, J= 10.0 Hz), 7.83 (1H, d, J= 5.0 Hz), 8.08(1H, d, J= 5.0 Hz) ppm; 13C NMR (176 MHz, DMSO-d6) δ 15.7, 26.2, 27.1, 58.6, 61.6, 64.6, 67.4, 84.6, 87.4, 108.0, 108.8, 121.9, 123.8, 125.7, 126.0, 126.4, 126.7, 127.2, 127.3, 127.8, 128.4, 129.1, 130.6, 133.1, 136.8, 137.5, 143.3, 144.6, 176.6, 179.7, 196.6 ppm. Declarations Acknowledgements We gratefully acknowledge the Research Affairs Division Sharif University of Technology (SUT), Islamic Republic of Iran support. Author contributions F.M.M. is in charge of overall direction and planning. B.A. devised the project and performed the experiments, analyzed spectra, and wrote the original draft. L.K. performed experiments and wrote the original draft. S.B. performed experiments and wrote the original draft. All authors reviewed the manuscript. Competing interests The authors declare no competing interests. Additional information Supplementary information accompanies this paper. Data availability All data generated or analyzed during this study are included in this article [and its supplementary information files]. Crystallographic model data is available through the CCDC under identifier 2327735. References Nivetha, N., Patil, S. M., Ramu, R., Sreenivasa, S., & Velmathi, S. 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Chem. 15 , 1961-1964 (2017). ‏ Chowdhury, R., Kumar, M., & Ghosh, S. K. Organocatalyzed enantioselective Michael addition/cyclization cascade reaction of 3-isothiocyanato oxindoles with arylidene malonates. Org. Biomol. Chem. 14 , 11250-11260 (2016). ‏ Sun, J., Xie, Y. J., & Yan, C. G. Construction of dispirocyclopentanebisoxindoles via self-domino Michael-aldol reactions of 3-phenacylideneoxindoles. J. Org. Chem. 78 , 8354-8365 (2013). ‏ Moghaddam, F. M., Aghamiri, B., & Badpa, S. Regio-and diastereoselective synthesis of new dispirocyclopentanebisoxindoles using a three-component strategy. Tetrahedron, 141 , 133495 (2023). ‏ Moghaddam, F. M., & Aghamiri, B. Facile one-pot, multi-component reaction to synthesize spirooxindole-annulated thiopyran derivatives under environmentally benevolent conditions. Heliyon. 8 (2022). Matloubi Moghaddam, F., Kavoosi, L., & Aghamiri, B. Facile one-pot, domino reaction to synthesize (Z)-2-imino-5-(1-alkyl-2-oxoindolin-3-ylidene) thiazolidin-4-one derivatives and its DFT study for the E/Z confirmation structure. Synth. Commun. 53 , 1153-1163 (2023). ‏ Alizadeh, A., & Mokhtari, J. (2011). A Novel, One‐Pot Four‐Component Route to 2′‐Thioxo‐2′, 3′‐dihydrospiro [indole‐3, 6′‐[1, 3] thiazin]‐2‐one Derivatives. Helv. Chim. Acta. 94 , 1315-1319 (2011) Tables Tables 1 and 2 are available in the Supplementary Files section. Schemes Schemes 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx Scheme1.jpg Scheme1. A comparative overview of the employed synthetic process in the previous and this work Scheme2.jpg Scheme 2.Proposed mechanism for the formation of final products Scheme3.jpg Scheme 3. Study on catalytic asymmetric induction Scheme4.jpg Scheme 4. 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1","display":"","copyAsset":false,"role":"figure","size":38095,"visible":true,"origin":"","legend":"\u003cp\u003eSingle-crystal structure of 3c and 5g.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/4025b89a8f8668931eb32a9d.jpg"},{"id":58824580,"identity":"8bb8d435-3a6e-40b1-a615-ef94ae73998d","added_by":"auto","created_at":"2024-06-21 17:23:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":874528,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/ec4e3125-4386-4089-b281-aa3a243c9cf9.pdf"},{"id":56554117,"identity":"83858191-061f-487c-b4f4-559d743850ca","added_by":"auto","created_at":"2024-05-15 16:56:16","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":449926,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/d95f1d51d6694659083b792b.docx"},{"id":56554115,"identity":"3a157c46-fd1d-463d-b779-1f2bf8c288cc","added_by":"auto","created_at":"2024-05-15 16:56:16","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":54707,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme1.\u003c/strong\u003e A comparative overview of the employed synthetic process in the previous and this work\u003c/p\u003e","description":"","filename":"Scheme1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/7df9019a2d778cb3a5ce3ea8.jpg"},{"id":56554224,"identity":"0566ff6b-fa3e-43fa-aa80-ee8e095dab3e","added_by":"auto","created_at":"2024-05-15 17:04:16","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":65076,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 2.\u003c/strong\u003eProposed mechanism for the formation of final products\u003c/p\u003e","description":"","filename":"Scheme2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/203d6d24795ffe6d43f76bff.jpg"},{"id":56554119,"identity":"4f44f016-ddbe-4cf6-90ba-7fd96a4647e8","added_by":"auto","created_at":"2024-05-15 16:56:16","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":35208,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 3.\u003c/strong\u003e Study on catalytic asymmetric induction\u003c/p\u003e","description":"","filename":"Scheme3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/9d4e85de8aba669c277a3e6c.jpg"},{"id":56554225,"identity":"c61a47ad-62b7-4619-96a2-7b90c2ffaedb","added_by":"auto","created_at":"2024-05-15 17:04:16","extension":"jpg","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":32009,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 4. \u003c/strong\u003eScale-up Reaction\u003c/p\u003e","description":"","filename":"Scheme4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/de606bd2c14e459afe6a8ec2.jpg"},{"id":56554121,"identity":"c0f49cec-6887-4feb-bc12-f9d7b4304c49","added_by":"auto","created_at":"2024-05-15 16:56:16","extension":"jpg","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":58525,"visible":true,"origin":"","legend":"","description":"","filename":"Graphicalabstract.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/f2c6466c6c0e55628ad7f3c6.jpg"},{"id":56554122,"identity":"1794f130-6da3-4415-b45b-089095a4cdac","added_by":"auto","created_at":"2024-05-15 16:56:16","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":7417625,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4306039/v1/461386499a5030c44d24efea.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Regio- and diastereoselective synthesis of thioxothiazolidin- indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e3-Alkenyl-oxindoles are pharmacologically advantageous scaffolds that have many biological properties. The widespread occurrence of 3-alkenyl-oxindoles at the heart of many plant-based alkaloids and natural products has further reinforced their merit in organic and medicinal chemistry.\u003csup\u003e1\u0026ndash;5\u003c/sup\u003eIn recent decades, 3-alkenyl oxindoles have been widely investigated, and detailed works have been done for transforming 3-alkenyl oxindoles into novel functionalized heterocycles.\u003csup\u003e6\u0026ndash;10\u003c/sup\u003e For instance, very recently, Li et al. described a procedure for the construction of sp\u003csup\u003e2\u003c/sup\u003e C\u0026ndash;N bond between 3-alkenyl oxindoles and indazole/benzotriazole.\u003csup\u003e11\u003c/sup\u003e In 2023, Mainkar et al. reported proline-catalyzed diastereoselective synthesis of dihydroquinolinyl-spirooxindole via aza-Michael/aldol reaction of 3-alkenyl oxindole.\u003csup\u003e12\u003c/sup\u003e In 2023, Song and coworkers described the synthesis of 3-alkenyl-2-oxindoles via a transition-metal-free [4\u0026thinsp;+\u0026thinsp;1] cyclization pathway.\u003csup\u003e13\u003c/sup\u003e Again in 2023, Stephan et al. developed a metal-free, B(C\u003csub\u003e6\u003c/sub\u003eF\u003csub\u003e5\u003c/sub\u003e(\u003csub\u003e3\u003c/sub\u003e catalyzed cyclopropanation of 3-alkenyl-oxindoles with diazomethanes.\u003csup\u003e14\u003c/sup\u003e Copper-catalyzed hydroboration of these compounds was also reported by Moro and coworkers.\u003csup\u003e15\u003c/sup\u003e According to other reports, 3-alkenyl oxindoles could easily converted to dispirooxindoles.\u003csup\u003e16\u0026ndash;21\u003c/sup\u003e For example, the synthesis of dispirocyclopentanebisoxindoles via sequential Michael-aldol reaction of 3-alkenyl oxindoles was reported by Yan and coworkers.\u003csup\u003e22\u003c/sup\u003e As another example, very recently our research group described a facile reaction for transforming 3-alkenyl oxindoles to dispirocyclopentanebisoxindoles.\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOn the other hand, from the distant past to the present, S-heterocycles have maintained their importance as an essential part and core of FDA-approved drugs and medicinally active molecules. A straightforward approach to synthesizing S-heterocycles is exploiting dithiocarbamates.\u003csup\u003e24\u0026ndash;25\u003c/sup\u003eThe great nucleophilic strength of dithiocarbamates has made them widely used in organic transformations. For example, Alizadeh and coworkers reported a thermodynamic approach for synthesizing 2\u0026rsquo;,3\u0026rsquo;-dihydro-2\u0026rsquo;-thioxospiro[indole-3,6\u0026rsquo;-[1,3]-thiazin]-2(1\u003cem\u003eH\u003c/em\u003e)-ones derivatives using dithiocarbamates at reflux conditions.\u003csup\u003e26\u003c/sup\u003e Unexpectedly, when we checked the above reaction at room temperature, we found that the final products are completely different from the previous work, and at room temperature, the reaction seems to be under kinetic control that leads to the formation of novel thioxothiazolidin-indolin-2-ones molecules. In addition to this, we found that the final products (thioxothiazolidin-indolin-2-ones) easily convert to dispirocyclopentanebisoxindoles under basic conditions, the same as 3-alkenyl oxindoles and our previous work (Scheme 1).\u003c/p\u003e \u003cp\u003eAs a result of what we have mentioned above, in this publication, we would like to report a kinetically controlled reaction for synthesizing novel thioxothiazolidin-indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion to dispirocyclopentanebisoxindoles. This synthetic procedure provides a feasible approach for synthesizing novel\u003c/p\u003e \u003cp\u003eorganic molecules bearing oxindole cores that might have future medicinal applications and the obtained molecules could be suitable for drug screening.\u003c/p\u003e \u003cp\u003e \u003cb\u003eScheme1.\u003c/b\u003e A comparative overview of the employed synthetic process in the previous and this work\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"2. Results and discussion","content":"\u003cp\u003eInitially, we investigated the four-component reaction of \u003cem\u003eN\u003c/em\u003e-allyl isatin \u003cstrong\u003e1a\u003c/strong\u003e, phosphonium ylide \u003cstrong\u003e2\u003c/strong\u003e, carbon disulfide, and methylamine as the model reaction (\u003cstrong\u003eTable 1\u003c/strong\u003e). Thus, a mixture of \u003cstrong\u003e1\u0026nbsp;\u003c/strong\u003e(0.3 mmol), \u003cstrong\u003e2\u003c/strong\u003e(0.3 mmol) in EtOH (2.0 mL) was mixed and stirred at room temperature for 30 min, then methylamine (0.3 mmol) and carbon disulfide (0.3 mmol) were added and stirred for more 1.5 h to afford 1-allyl-4-hydroxy-3-methyl-4-phenyl-2-thioxothi- azolidin-5-yl)indolin-2-one (\u003cstrong\u003e3a\u003c/strong\u003e) in satisfactory yield. Then, several solvents were assessed to achieve the optimal reaction conditions. The reaction proceeded slowly in DMSO, CHCl\u003csub\u003e3\u003c/sub\u003e, CH\u003csub\u003e3\u003c/sub\u003eCN, and CH\u003csub\u003e2\u003c/sub\u003eCl\u003csub\u003e2\u003c/sub\u003e with unsatisfactory yield (\u003cstrong\u003eTable 1, entries 1-4\u003c/strong\u003e). Furthermore, the reaction failed to occur in H\u003csub\u003e2\u003c/sub\u003eO and THF (\u003cstrong\u003eTable 1, entries 5, 6\u003c/strong\u003e). In complete contrast, the reaction yield increased greatly in alcoholic solvents such as n-Octanol, MeOH, and PrOH, especially in EtOH (\u003cstrong\u003eTable 1, entries 7-12\u003c/strong\u003e). PEG-400 was not as good as alcoholic solvents (\u003cstrong\u003eTable 1, entry 10\u003c/strong\u003e). We found that the reaction proceeded well under catalyst-free conditions and at room temperature. These results prompted us to further screen the reaction conditions. In the next step of synthetic work, we considered the formation of product \u003cstrong\u003e3a\u0026nbsp;\u003c/strong\u003eunder reflux conditions (\u003cstrong\u003eTable 1, entry 12\u003c/strong\u003e). We found that reflux conditions prevent product 3a formation (\u003cstrong\u003eplease refer to Scheme 1\u003c/strong\u003e). Hence, the best results for synthesizing product \u003cstrong\u003e3a\u003c/strong\u003e were obtained at 25 \u0026ordm;C under catalyst-free conditions and after 2 h of stirring (\u003cstrong\u003eTable 1, entry 11\u003c/strong\u003e). The general procedure used for synthesizing product \u003cstrong\u003e3a\u003c/strong\u003e was also employed for compound \u003cstrong\u003e4a\u003c/strong\u003e, except using dimethylamine in place of methylamine (\u003cstrong\u003eTable 1, entry 13\u003c/strong\u003e). To our surprise, products \u003cstrong\u003e3a\u003c/strong\u003e and \u003cstrong\u003e4a\u003c/strong\u003e were easily converted to dispirocyclopentanebisoxindoles (\u003cstrong\u003e5a-5d\u003c/strong\u003e) under basic conditions (\u003cstrong\u003eTable 1, entries 15-25\u003c/strong\u003e). This conversion proceeded well in the presence of different bases such as LDA, KOH, NaOH, and K\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e via one-pot operation after 30-90 min of stirring. In contrast, Et\u003csub\u003e3\u003c/sub\u003eN converted products \u003cstrong\u003e3a\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003e4a\u003c/strong\u003e to isatin chalcone and was not able to convert \u003cstrong\u003e3a\u003c/strong\u003e and \u003cstrong\u003e4a\u003c/strong\u003e to dispirocyclopentanebisoxindole products (\u003cstrong\u003eTable 1, entry 26\u003c/strong\u003e). In the next step of synthetic work, with the optimal reaction conditions in hand, the generality for substrates was also studied (\u003cstrong\u003eTable 2\u003c/strong\u003e). Most functional groups were tolerable and the reaction was carried out successfully with various substituents on the nitrogen and the aromatic ring of the isatin. Moreover, the reaction gave satisfactory answers with different aromatic and aliphatic amines. \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR, FT-IR, and elemental analysis determined the structure of the final products. Compound 3c and 5g were also crystallized from EtOAc by slow evaporation at room temperature and the structure was confirmed by \u003cem\u003eX\u003c/em\u003e-ray crystallographic analysis (\u003cstrong\u003eFigure 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eTo understand the sequence of steps of the reaction, we proposed a plausible mechanism as illustrated in Scheme 2. In the beginning, isatin derivatives reacted with phosphonium ylide to form isatin chalcone \u003cstrong\u003eA\u003c/strong\u003e. In addition, carbamodithioic acid \u003cstrong\u003eB\u0026nbsp;\u003c/strong\u003ecould be resulted from the addition of the amine to carbon disulfide. Subsequent attack of the carbamodithioic acid B on isatin chalcone \u003cstrong\u003eA\u003c/strong\u003e lead to the formation of intermediate \u003cstrong\u003eC\u003c/strong\u003e. \u0026nbsp; Finally, the intramolecular attack on the carbonyl yields the final thioxothiazolidin-indolin-2-one products. Following, in basic media, the thioxothiazolidin-indolin-2-one could be converted to dispirocyclopentanebisoxindoles via sequential condensation, Michael addition, and intramolecular cyclization reaction.\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eScheme 2.\u003c/strong\u003e Proposed mechanism for the formation of final products\u003c/p\u003e\n\u003cp\u003eThe products \u003cstrong\u003e3a-3w\u003c/strong\u003e and \u003cstrong\u003e5a-5g\u003c/strong\u003e were racemic mixtures (0 % ee value) owing to the lack of chiral inducing agents. To obtain the related enantiomeric products in unequal amounts, we used the (-)-quinine (\u003cstrong\u003e6\u003c/strong\u003e, 30 mol%) as a chiral catalyst. Unfortunately, all our attempts to induce enantioselectivity and obtain the asymmetric version of the final products failed (Scheme 3). \u0026nbsp;To show that these synthetic procedures are certainly worthwhile, we eventually tested the gram scale synthesis of products \u003cstrong\u003e3a\u003c/strong\u003e and \u003cstrong\u003e5a\u003c/strong\u003e (Scheme 4). For this reason, to a solution of \u003cem\u003eN-\u003c/em\u003eallyl isatin (\u003cstrong\u003e1a\u003c/strong\u003e, 6.0 mmol, 1.12 g) in MeOH, phosphonium ylide (\u003cstrong\u003e2,\u0026nbsp;\u003c/strong\u003e6.0 mmol, 1.53 g) was added and stirred at room temperature for 30 min to afford the corresponding isatin chalcone. In the next step, carbon disulfide (6.0 mmol, 0.36 mL) and methylamine (6.0 mmol, 0.52 mL) were added to the reaction mixture and stirred for more 1.5 h to form product \u003cstrong\u003e3a\u003c/strong\u003e. Upon completion of the reaction, the reaction color changes from red to pale yellow. \u0026nbsp;In this stage, we added KOH (0.8 equiv.) to form dispirocyclopentanebisoxindole (\u003cstrong\u003e5a\u003c/strong\u003e). After completion of the reaction, the organic products were simply filtered off and the precipitate was washed with EtOH.\u003c/p\u003e\n\u003cp\u003eWe were delighted to obtain the products \u003cstrong\u003e3a\u003c/strong\u003e and \u003cstrong\u003e5a\u003c/strong\u003e in 71 and 76 % yield, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eScheme 3.\u003c/strong\u003e Study on catalytic asymmetric induction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eScheme 4.\u0026nbsp;\u003c/strong\u003eScale-up Reaction\u003c/p\u003e"},{"header":"3. Conclusion","content":"\u003cp\u003eIn this publication, we reported an efficient and facile synthesis of thioxothiazolidin-indolin-2-one and oxoindolin-carbamodihioate hybrids from isatin chalcones and achieved success in their base-catalyzed conversion into dispirocyclopentanebisoxindoles. The procedure exhibited great efficiency in providing final products with decent yields from accessible starting materials and displaying excellent regio- and diastereoselectivity. Short reaction time, mild reaction conditions, satisfying the green chemistry standards, easy reaction workup, a favorable response to gram-scale synthesis, excellent regio- and diastereoselectivity, readily accessible source of starting materials, and one-pot synthetic operation are some advantages of this work. \u0026nbsp;\u0026nbsp;\u003c/p\u003e"},{"header":"4. Experimental Section","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e4.1\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e. General Remarks.\u0026nbsp;\u003c/strong\u003eAll solvents and starting materials were purchased from Merck and Sigma-Aldrich used without any additional purification. Analytical TLC was carried out using Merck 0.2 mm silica gel 60 F-254 Al-plates. \u003csup\u003e1\u003c/sup\u003eH NMR and \u003csup\u003e13\u003c/sup\u003eC NMR spectra were recorded on a Bruker Avance DRX-500 machine using DMSO-\u003cem\u003ed\u003csub\u003e6\u003c/sub\u003e\u003c/em\u003e as solvent and TMS as an internal standard at room temperature (DMSO-\u003cem\u003ed\u003csub\u003e6\u003c/sub\u003e\u003c/em\u003e \u003csup\u003e1\u003c/sup\u003eH NMR: \u003cem\u003eδ\u003c/em\u003e (ppm) =2.50 ppm; \u003csup\u003e13\u003c/sup\u003eC NMR: \u003cem\u003eδ\u003c/em\u003e (ppm) =39.9 ppm; CDCl\u003csub\u003e3\u003c/sub\u003e \u003csup\u003e1\u003c/sup\u003eHNMR: \u003cem\u003eδ\u003c/em\u003e (ppm) = 7.26 and \u003csup\u003e13\u003c/sup\u003eC-NMR: \u003cem\u003eδ\u003c/em\u003e (ppm) = 77.00 ppm). Chemical shifts were reported in ppm scale. FT-IR spectra of samples were obtained on ABB Bomem MB100 spectrometer with potassium bromide (KBr) pellets. Melting points were determined using an Electrothermal 9100 apparatus and are uncorrected. Elemental analysis was done by LECO Truspec.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e4.2.\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Experimental procedure for the synthesis of compounds 3 (3a-3w), 4 (4a-4d), and 5 (5a-5g).\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo a solution of isatin derivatives (\u003cstrong\u003e1a-1w\u003c/strong\u003e, 0.3mmol) in alcoholic solvents (2.0 mL), phosphonium ylide (\u003cstrong\u003e2,\u0026nbsp;\u003c/strong\u003e0.3 mmol) was added and stirred at room temperature for 30 min to afford the corresponding isatin chalcone. Upon completion of the reaction, the reaction color changes from orange to red. In the next step, carbon disulfide (0.3 mmol) and primary (1°) amines (0.3 mmol) were added to the reaction mixture and stirred for more 1.5 h to form products \u003cstrong\u003e3a-3w\u003c/strong\u003e (the general procedure used for synthesizing the products \u003cstrong\u003e3a-3w\u003c/strong\u003e was also employed for compounds \u003cstrong\u003e4a-4d\u003c/strong\u003e,except using secondary (2°) amines in place of primary (1°) amines). Upon completion of the reaction, the reaction color changes from red to pale yellow. In this stage, if we added KOH (15 mg, 0.8 equiv.) to the reaction mixture, products \u003cstrong\u003e3\u003c/strong\u003e or \u003cstrong\u003e4\u003c/strong\u003e easily converted to dispirocyclopentane- \u0026nbsp; bisoxindoles (\u003cstrong\u003e5a-5g\u003c/strong\u003e) after 30-90 min of stirring (first, the reaction color changes from pale yellow to red, and then from red to white). After completion of the reaction, the organic products were simply filtered off and the precipitate was washed with EtOH. The pure products were dried in air and directly characterized by \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR, elemental and FT-IR analysis. In addition,\u0026nbsp;the structure of compound \u003cstrong\u003e3c\u003c/strong\u003e was confirmed by \u003cem\u003eX\u003c/em\u003e-ray crystallographic analysis.\u003c/p\u003e\n\u003cp\u003e1-allyl-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3a)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (96 mg, 81 %); m.p. 178-180 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.09 (3H, s), 4.35 (1H, d.d., \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.44 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.46 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.53 (1H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.33 (2H, quintet, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.87 (1H, m), 6.93 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.08 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.31 -7.59 (6H, m), 8.15 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 32.7, 43.2, 46.9, 56.8, 100.2, 110.2, 118.6, 123.7, 123.8, 124.8, 125.4, 129.2, 129.3, 129.4, 130.2, 141.8, 143.5, 176.5, 191.4 ppm; IR (KBr) ν= 3300-3080, 1675, 1640, 1609 cm\u003csup\u003e-1\u003c/sup\u003e; \u0026nbsp;Anal.\u003c/p\u003e\n\u003cp\u003eCalcd. for C\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e20\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 63.61; H, 5.08; N, 7.06; Found: C, 63.45; H, 5.16; N, 6.75 %.\u003c/p\u003e\n\u003cp\u003e1-benzyl-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3b)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (112 mg, \u0026nbsp; 84 %); m.p. 160-162 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.12 (3H, s), 4.46 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.52 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.79 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.23 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.81 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.05 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.23 -7.62 (11H, m), 8.19 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 32.7, 44.8, 47.0, 56.9, 100.2, 110.4, 123.7, 123.8, 124.7, 125.4, 127.6, 128.1, 129.1, 129.2, 129.3, 129.4, 134.5, 141.8, 143.5, 176.9, 191.4 ppm; IR (KBr) ν= 3300-3161, 1675, 1614 cm\u003csup\u003e-1\u003c/sup\u003e; Anal. Calcd. for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 67.24; H, 4.97; N, 6.27; Found: C, 67.01; H, 5.11; N, 6.08 %.\u003c/p\u003e\n\u003cp\u003e3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3c)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (102 mg, 86 %); m.p. 172-174 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.04 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 1.78 (2H, m), 3.09 (3H, s), 3.69 (1H, m), 3.86 (1H, m), 4.42 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.43 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.96 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp;7.08 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.34 -7.60 (6H, m), 8.27 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 11.6, 20.8, 32.7, 42.6, 46.8, 56.8, 100.2, 109.6, 123.6, 123.8, 124.7, 124.8, 125.6, 129.2, 129.4, 141.9, 143.9, 176.7, 191.4 ppm; IR (KBr) ν= \u0026nbsp;3300-3050, 1670, 1609 cm\u003csup\u003e-1\u003c/sup\u003e; \u0026nbsp;Anal. Calcd. for C\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 63.29; H, 5.56; N, 7.03; Found: C, 62.97; H, 5.68; N, 6.87 %\u003c/p\u003e\n\u003cp\u003e5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3d)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (100 mg, 77 %); m.p. 150-152 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.03 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 5.0 Hz), 1.76 (2H, m), 3.08 (3H, s), 3.66 (1H, m), 3.84 (1H, m), 4.37 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.42 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.88 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp;7.08 (1H, s), 7.33 -7.57 (6H, m), 8.06 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 11.5, 20.8, 32.7, 42.8, 46.9, 56.6, 100.1, 100.2, 110.5, 124.3, 124.7, 127.2, 129.3, 129.4, 129.5, 141.6, 142.5, 176.2, 191.1 ppm; IR (KBr) ν =\u0026nbsp;3300-3056, 1675, 1609 cm\u003csup\u003e-1\u003c/sup\u003e; Anal. Calcd. for C\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 58.25; H, 4.89; N, 6.47; Found: C, 58.01; H, 5.04; N, 6.21 %\u003c/p\u003e\n\u003cp\u003e1-allyl-5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3e)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (107 mg, 83 %); m.p. 154-156 °C;\u0026nbsp;\u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.08 (3H, s), 4.32 (1H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.39 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.47 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.54 (1H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.33 (2H, quintet, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.84 (1H, m), 6.86 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp;7.09 (1H, s), 7.31 -7.58 (6H, m), 7.95 (1H, s) \u0026nbsp; ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 32.8, 43.3, 46.9, 56.6, 100.2, 111.2, 118.9, 124.3, 124.7, 127.1, 129.3, 129.4, 129.9, 141.5, 156.7, 176.5, 191.0 ppm; IR (KBr) ν= \u0026nbsp; 3300-3086, 1672, 1643, 1612 \u0026nbsp;cm\u003csup\u003e-1\u003c/sup\u003e; \u0026nbsp;Anal. Calcd. for C\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e19\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 58.53; H, 4.44; N, 6.50; Found: C, 58.22; H, 4.51; N, 6.35 %.\u003c/p\u003e\n\u003cp\u003e1-benzyl-5-chloro-3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3f)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (114 mg, 79 %); m.p. 128-130 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.12 (3H, s), 4.41 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.54 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.75 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.23 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.73 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.03 (1H, s), 7.21 -7.60(11H, m), 7.99 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 32.8, 44.9, 47.1, 56.7, 100.2, 111.3, 124.2, 124.7, 127.1, 127.6, 128.3, 129.2, 129.3, 129.4, 129.5, 129.5, 134.0, 141.5, 142.0, 176.5, 191.0 ppm; IR (KBr) ν= 3350-3100, 1678, 1615 cm\u003csup\u003e-1\u003c/sup\u003e; Anal. Calcd. for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 62.42; H, 4.40; N, 5.82; Found: C, 62.15; H, 4.53; N, 5.65%.\u003c/p\u003e\n\u003cp\u003e3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3g)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (101 mg, 91 %); m.p. 170-172 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.09 (3H, s), 3.33 (3H, s), 4.43 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.45 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.94 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.09 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.36 -7.59 (6H, m), 8.26 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 27.0, 32.8, 46.9, 56.7, 100.2, 109.3, 123.6, 123.9, 124.7, 125.3, 129.2, 129.3, 129.5, 142.0, 144.3, 176.6, 191.5 ppm; IR (KBr) ν=\u0026nbsp;3400-3150, 1676, 1604 \u0026nbsp;cm\u003csup\u003e-1\u003c/sup\u003e; \u0026nbsp;Anal. Calcd. for C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 61.60; H, 4.90; N, 7.56; Found: C, 61.35; H, 4.96; N, 7.41 %\u003c/p\u003e\n\u003cp\u003e3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3h)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (93 mg, 87 %); m.p. 164-166 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.09 (3H, s), 4.44 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.46 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.98 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.07 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.32 -7.59 (6H, m), 7.88 (1H, s), 8.10 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 32.8, 47.3, 56.7, 100.2, 109.6, 123.8, 124.0, 124.7, 125.9, 129.3, 129.4, 129.5, 141.2, 141.7, 178.4, 191.7 ppm; IR (KBr) ν= \u0026nbsp;3350,\u0026nbsp;3300-3150, 1673, 1610 cm\u003csup\u003e-1\u003c/sup\u003e; \u0026nbsp;Anal. Calcd. for C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 60.65; H, 4.52; N, 7.86; Found: C, 60.53; H, 4.60; N, 7.75 %\u003c/p\u003e\n\u003cp\u003e3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-isopropylindolin-2-one (3i)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (110 mg, 92%); m.p. 180-182 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.56 (6H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.09 (3H, s), 4.36 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.38 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.63 (1H, septet, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), \u0026nbsp;7.06 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.10 (1H, d, , \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.32 -7.58 (6H, m), 8.32 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 19.3, 19.6, 32.7, 45.4, 46.7, 57.4, 100.2, 110.8, 123.3, 123.9, 124.8, 125.9, 129.3, 129.3, 141.8, 143.2, 176.5, 191.5 ppm; Anal. Calcd. for C\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 63.29; H, 5.56; N, 7.03; Found: C, 63.13; H, 5.64; N, 6.85 %\u003c/p\u003e\n\u003cp\u003eEthyl-2-(3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-2-oxoindolin-1-yl)acetate (3j)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (126 mg, 95%); m.p. 142-144 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.31 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.08 (3H, s), 4.28 (2H, q, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.42 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 4.47 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.53 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.68 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 6.83 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp;7.12 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.30 -7.61 (6H, m), 7.88 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 14.3, 32.8, 42.1, 46.8, 56.6, 62.3, 100.2, 109.3, 123.9, 124.2, 124.8, 125.1, 129.3, 129.3, 129.5, 141.8, 143.0, 166.8, 176.9, 191.6 \u0026nbsp;ppm; Anal. Calcd. for C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 59.71; H, 5.01; N, 6.33; Found: C, 59.63; H, 5.11; N, 6.21 %\u003c/p\u003e\n\u003cp\u003e3-(4-hydroxy-3-methyl-4-phenyl-2-thioxothiazolidin-5-yl)-1-(naphthalen-1-ylmethyl) indolin-2-one (3k)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (119 mg, 80%); m.p. 176-178 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.11 (3H, s), 4.52 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.61 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.44 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.57 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.74(1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.05-7.21 (3H,m), 7.44-7.69 (9H, m), 7.84 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.94 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 8.11 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz) 8.22 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 32.8, 42.7, 47.2, 56.9, 100.3, 110.6, 122.6, 123.7, 124.0, 124.7, 124.8, 125.5, 126.0, 126.1, 126.9, 128.6, 129.1, 129.2, 129.3, 129.4, 129.5, 130.9, 133.9, 141.8, 143.8, 177.1, 191.3 ppm; Anal. Calcd. for C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 70.13; H, 4.87; N, 5.64; Found: C, 69.97; H, 5.04; N, 5.49%\u003c/p\u003e\n\u003cp\u003e1-benzyl-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3l)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (114 mg, 83 %); m.p. 152-154 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.29 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.35 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.94 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.42 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.52 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.79 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.25 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 6.82 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.06 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.18 -7.65 (11H, m), 8.26 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 13.4, 42.3, 44.7, 47.1, 57.0, 100.9, 110.3, 123.7, 123.8, 124.8, 125.5, 127.6, 128.1, 129.1, 129.2, 129.3, 129.4, 134.5, 142.6, 143.6, 177.0, 190.8 ppm; Anal. Calcd. for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 67.80; H, 5.25; N, 6.08; Found: C, 67.61; H, 5.37; N, 5.93 %.\u003c/p\u003e\n\u003cp\u003e1-allyl-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3m)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (93 mg, 76 %); m.p. 136-138 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.26 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 3.32 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.90 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.37 (1H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.41 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.46 (1H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.51 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.33 (2H, quintet, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.85 (1H, m), 6.92 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp;7.09 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.34 -7.62 (6H, m), 8.20 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 13.4, 42.3, 43.1, 47.0, 56.9, 100.9, 110.1, 118.5, 123.7, 123.8, 124.8, 125.4, 129.1, 129.3, 129.4, 130.2, 142.6, 157.5, 176.5, 190.8 ppm; Anal. Calcd. for C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 64.36; H, 5.40; N, 6.82; Found: C, 64.27; H, 5.51; N, 6.68 %.\u003c/p\u003e\n\u003cp\u003e3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3n)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (91 mg, 74 %); m.p. \u0026nbsp;140-142 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.04 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 1.26 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 1.79 (2H, m), 3.32 (1H, m), 3.72 (1H, m), 3.89 (2H, m), 4.39 (1H, d,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 5.0 Hz), \u0026nbsp;4.41 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.95 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.07 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.26 -7.62 (6H, m), 8.34 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 11.6, 13.4, 20.8, 40.2, 42.6, 47.0, 56.9, 100.9, 109.6, 123.6, 123.8, 124.8, 125.6, 129.1, 129.2, 129.4, 142.7, 144.0, 176.7, 190.9 ppm; Anal. Calcd. for C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 64.15; H, 5.86; N, 6.79; Found: C, 63.81; H, 5.92; N, 6.58 %\u003c/p\u003e\n\u003cp\u003e5-chloro-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3o)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (114 mg, 85 %); m.p. 134-136 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.03 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 1.25 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 1.78 (2H, m), 3.30 (1H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 5.0 Hz), 3.68 (1H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 5.0 Hz), 3.88 (2H, m), 4.32 (1H, , d,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 5.0 Hz), 4.42 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.88 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp; 7.07 (1H, s), 7.32 -7.60 (6H, m), 8.12 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 11.5, 13.3, 20.8, 42.3, 42.7, 47.0, 56.7, 100.9, 110.5, 121.4, 124.3, 124.7, 129.2, 129.4, 142.4, 156.2, 176.3, 190.5 ppm; Anal. Calcd. for C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e23\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 59.11; H, 5.19; N, 6.27; Found: C, 58.93; H, 5.24; N, 6.12 %\u003c/p\u003e\n\u003cp\u003eethyl-2-(3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-2-oxoindolin-1-yl)acetate (3p)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (103 mg, 75 %); m.p. 138-140 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.26 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 1.32 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.30 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.91 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.28 (2H, q, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.40 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 4.44 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.53 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.73 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 6.83 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.10 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.33 -7.61 (6H, m), 7.91 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 13.4, 14.3, 42.1, 42.3, 47.0, 56.6, 62.3, 100.9, 109.3, 123.9, 124.1, 124.8, 125.1, 129.2, 129.3, 129.5, 142.6, 143.1, 166.9, 176.9, 191.0 ppm; Anal. Calcd. for C\u003csub\u003e23\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 60.51; H, 5.30; N, 6.14; Found: C, 60.38; H, 5.42; N, 5.97 %\u003c/p\u003e\n\u003cp\u003e1-benzyl-5-chloro-3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3q)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (121 mg, 82 %); m.p. 198-200 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.57 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.53 (2H, q, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.94 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.16 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.99 (2H, s), 6.66 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.14 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.27 -7.63 (10H, m), 8.02 (1H,s) 8.04 (1H, s) ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 39.9, 41.3, 44.2, 110.0, 125.0, 127.3, 127.8, 127.9, 128.0, 128.3, 128.3, 128.8, 129.0, 130.8, 133.7, 135.5, 142.1, 177.4, 196.5 ppm; Anal. Calcd. for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e23\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 63.08; H, 4.68; N, 5.66; Found: C, 62.81; H, 4.76; N, 5.41 %\u003c/p\u003e\n\u003cp\u003e3-(3-ethyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3r)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (106 mg, 92 %); m.p. 140-142 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.27 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.30 (1H, m), 3.34 (3H, s), 3.90 (1H, m), 4.42 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.43 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.94 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp; 7.09 (2H, m), 7.38 -7.62 (6H, m), 8.30 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 13.4, 27.0, 42.3, 47.1, 56.7, 101.0, 109.3, 123.6, 123.8, 124.8, 125.3, 129.1, 129.3, 129.5, 142.8, 144.3, 176.7, 190.9 ppm; Anal. Calcd. for C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e20\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 62.47; H, 5.24; N, 7.29; Found: C, 62.21; H, 5.33; N, 7.10 %\u003c/p\u003e\n\u003cp\u003e3-(-3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-propylindolin-2-one (3s)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (125 mg, \u0026nbsp; 88 %); m.p. 130-132 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 1.07 (3H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 1.81 (2H, m), 3.70 (1H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 3.87(1H, t,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz), 4.36 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.48 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.52 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.12 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.95 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.07 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.20 -7.59 (11H, m), 8.25 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 11.7, 20.9, 42.6, 46.7, 50.2, 57.0, 101.0, 109.6, 123.6, 123.8, 125.0, 125.5, 127.0, 128.0, 128.4, 129.0, 129.2, 129.5, 136.7, 142.6, 143.9, 176.5, 193.0 ppm; Anal. Calcd. for C\u003csub\u003e27\u003c/sub\u003eH\u003csub\u003e26\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 68.33; H, 5.52; N, 5.90; Found: C, 68.10; H, 5.61; N, 5.76 %.\u003c/p\u003e\n\u003cp\u003e3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-methylindolin-2-one (3t)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (122 mg, \u0026nbsp; 91 %); m.p. 140-142 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.34 (3H, s), 4.38 (1H, d, , \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.48 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.51 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.14 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.93 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.09 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.21-7.59 (11H, m), 8.17 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 27.1, 46.7, 50.3, 56.8, 101.1, 109.3, 123.7, 123.8, 125.0, 127.0, 128.0, 128.3, 129.0, 129.2, 129.6, 132.0, 136.6, 142.7, 144.3, 176.5, 193.1 ppm; Anal. Calcd. for C\u003csub\u003e25\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 67.24; H, 4.97; N, 6.27; Found: C, 66.98; H, 5.11; N, 6.03 %.\u003c/p\u003e\n\u003cp\u003e1-allyl-3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3u)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (123 mg, \u0026nbsp; 87 %); m.p. 132-134°C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 4.41 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.48 (1H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.50 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.52 (1H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.14 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.35 (2H, quintet, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.90 (1H, m), 6.93 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.08 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.20 -7.60 (11H, m), 8.09 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 43.1, 46.7, 50.2, 57.0, 101.0, 110.2, 118.6, 123.7, 125.0, 125.3, 127.0, 128.0 , 128.4, 129.0, 129.2, 129.4, 130.4, 136.6, 142.5, 143.5, 176.3, 193.0 ppm; Anal. Calcd. for C\u003csub\u003e27\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 68.62; H, 5.12; N, 5.93; Found: C, 68.43; H, 5.26; N, 5.78 %.\u003c/p\u003e\n\u003cp\u003e1-benzyl-3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl) indolin-2-one (3v)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (124 mg, \u0026nbsp; 79 %); m.p. 154-156 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 4.46 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.49 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.51 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.80 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.20 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.82 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.05 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.19 -7.62 (16H, m), 8.10 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 44.7, 46.8, 50.3, 57.0, 101.1, 110.2, 123.7, 123.8, 124.9, 125.4, 127.0, 127.6, 128.0, 128.1, 128.5, 129.0, 129.2, 129.2, 129.4, 134.7, 136.7, 142.6, 143.5, 176.7, 193.0 ppm; Anal. Calcd. for C\u003csub\u003e31\u003c/sub\u003eH\u003csub\u003e26\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 71.24; H, 5.01; N, 5.36; Found: C, 71.02; H, 5.12; N, 5.10 %.\u003c/p\u003e\n\u003cp\u003e3-(3-benzyl-4-hydroxy-4-phenyl-2-thioxothiazolidin-5-yl)-1-(naphthalen-1-ylmethyl) indolin-2-one (3w)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (132 mg, 77%); m.p. 140-142 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 4.49 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.52 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.56 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.19 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.43 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.58 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.75(1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp;7.05-7.69 (17H, m), 7.86 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.95 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 8.14 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz) 8.16 (1H, s) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 42.8, 47.0, 50.3, 56.9, 100.0, 101.1, 110.6, 122.7, 123.7, 123.9, 124.9, 125.0, 125.9, 126.2, 127.0, 127.0, 128.0, 128.3, 128.7, 129.1, 129.2, 129.3, 129.3, 129.5, 130.9, 133.9, 136.6, 142.6, 143.8, 176.9, 192.9 pm; Anal. Calcd. for C\u003csub\u003e35\u003c/sub\u003eH\u003csub\u003e28\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 73.40; H, 4.93; N, 4.89; Found: C, 73.27; H, 5.09; N, 4.71 %\u003c/p\u003e\n\u003cp\u003e1-(1-allyl-2-oxoindolin-3-yl)-2-oxo-2-phenylethyldimethyl- carbamodithioate (4a)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (102 mg, \u0026nbsp; 83 %); m.p. 114-116 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.38 (3H, s), 3.62 (3H, s), 3.92 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.47 (2H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.35 (2H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.97 (1H, quintet, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.84 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.01 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.25 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.43 -7.58 (4H, m), 8.02 (2H, d ,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 35.2, 42.5, 46.2, 57.5, 109.2, 117.8, 122.9, 126.6, 127.8, 128.5, 128.7, 128.9, 131.2, 131.7, 132.6, 133.9, 136.4, 137.7, 176.1, 191.3, 194.1 ppm;\u0026nbsp;Anal. Calcd. for C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 64.36; H, 5.40; N, 6.82; Found: C, 64.24; H, 5.48; N, 6.67 %.\u003c/p\u003e\n\u003cp\u003e1-(1-benzyl-2-oxoindolin-3-yl)-2-oxo-2-phenylethyldimethyl- carbamodithioate (4b)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (102 mg, \u0026nbsp; 74 %); m.p. 140-142 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.38 (3H, s), 3.63 (3H, s), 4.01 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.05 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.71 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.88 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.98 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.16 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.34 -7.59 (9H, m), 8.05 (2H, d ,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz) ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 41.7, 44.1, 46.3, 46.5, 57.5, 94.4, 109.1, 122.4, 123.9, 126.5, 127.5, 127.6, 128.5, 128.7, 129.0, 133.6, 134.9, 136.2, 143.6, 176.3, 194.2, 194.2 ppm; Anal. Calcd. for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 67.80; H, 5.25; N, 6.08; Found: C, 67.57; H, 5.37; N, 5.92%.\u003c/p\u003e\n\u003cp\u003e1-(1-allyl-5-chloro-2-oxoindolin-3-yl)-2-oxo-2-phenylethyl dimethylcarbamodithioate (4c)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (108 mg, 81 %); m.p. 110-112 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.39 (3H, s), 3.64 (3H, s), 3.90 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 4.45 (2H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.34 (2H, d.d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.95 (1H, quintet, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.79 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.20 (1H,d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.45 -7.60 (4H, m), 7.97 (2H, d ,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 41.6, 42.6, 46.2, 46.6, 57.5, 100.0, 109.9, 117.8, 124.2, 127.9, 128.4, 128.9, 129.3, 131.3, 132.2, 133.8, 134.7, 164.6, 184.5, 193.9 ppm; Anal. Calcd. for C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 59.38; H, 4.76; N, 6.30; Found: C, 59.22; H, 4.84; N, 6.21 %.\u003c/p\u003e\n\u003cp\u003e1-(1-benzyl-5-chloro-2-oxoindolin-3-yl)-2-oxo-2-phenylethyl dimethylcarbamodithioate (4d)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (119 mg, \u0026nbsp;80\u0026nbsp;%); m.p. 132-134 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 3.39 (3H, s), 3.99 (3H, s), 3.99 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 5.03 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.61 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 6.85 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.12(1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.35 -7.60 (9H, m), 8.01 (2H, d ,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 10.0 Hz) ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e) δ 41.7, 44.2, 46.4, 46.7, 57.5, 110.0, 124.3, 127.5, 127.7, 128.4, 128.8, 128.8, 129.0, 133.8, 134.6, 135.8, 142.2, 176.0, 193.9, 194.0 ppm; Anal. Calcd. for C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e23\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e: C, 63.08; H, 4.68; N, 5.66; Found: C, 62.81; H, 4.81; N, 5.49 %.\u003c/p\u003e\n\u003cp\u003e1,1''-diallyl-2'-benzoyl-4'-hydroxy-5'-methoxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5a)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (79 mg, 86 %); m.p. 258-260 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 2.95 (3H, s), 3.93 (2H, d.d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 4.21 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 4.53 (2H, d.d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 4.80 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.14 (1H, quintet, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.21 (2H, t, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.27 (1H, \u003cem\u003es\u003c/em\u003e), 5.77 (1H, quintet, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.96 (1H, \u003cem\u003es\u003c/em\u003e), 6.57 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 6.63 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 6.68 (1H, s), 6.98 -7.23 (13H, m), 7.374 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 7.86 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 8.06 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz) ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 41.9, 43.1, 58.3, 60.0, 60.7, 61.6, 84.5, 89.3, 100.0, 108.8, 109.4, 116.9, 118.4, 122.0, 123.9, 125.0, 125.9, 126.2, 126.6, 127.3, 127.6, 127.9, 129.1, 130.6, 131.6, 131.9, 133.3, 136.8, 137.6, 142.5, 143.8, 176.3, 179.3, 196.6 ppm; Anal. Calcd. for C\u003csub\u003e39\u003c/sub\u003eH\u003csub\u003e34\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e: C, 76.70; H, 5.61; N, 4.59; Found: C, 76.51; H, 5.76; N, 4.34 %;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2'-benzoyl-4'-hydroxy-1,1''-dimethyl-5'-(octyloxy)-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5b)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (88 mg, 89 %); m.p. 222-224 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, DMSO-d6) δ 0.79-1.19 (15H, m), 2.79 (3H,s), 2.85 (1H, t, \u003cem\u003eJ\u003c/em\u003e = 10.0 Hz), 3.08 (3H,s), 3.17 (1H, t, \u003cem\u003eJ\u0026nbsp;\u003c/em\u003e= 10.0 Hz), 5.22 (1H, s), 5.99 (1H, s), 6.56 (1H, d, \u003cem\u003eJ\u0026nbsp;\u003c/em\u003e= 5.0 Hz), 6.75 (2H, t, \u003cem\u003eJ\u003c/em\u003e = 5.0 Hz), 6.97 -7.49 (14H, m), 7.82 (1H, d, \u003cem\u003eJ\u003c/em\u003e = 5.0 Hz), 8.09 (1H, d, \u003cem\u003eJ\u003c/em\u003e = 5.0 Hz) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, DMSO-d6) δ 14.4, 22.5, 25.8, 26.2, 27.1, 28.9, 29.0, 29.6, 31.6, 58.5, 61.6, 64.6, 84.6, 87.5, 108.0, 108.8, 112.7, 122.0, 123.8, 125.7, 126.1, 126.4, 126.7, 127.2, 127.3, 127.8, 128.4, 129.1, 130.6, 131.6, 133.2, 136.8, 137.5, 143.3, 144.5, 176.6, 179.7, 196.6 ppm; Anal. Calcd. for C\u003csub\u003e42\u003c/sub\u003eH\u003csub\u003e44\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e: C, 76.80; H, 6.75; N, 4.27; Found: C, 76.64; H, 6.83; N, 4.08 %.\u003c/p\u003e\n\u003cp\u003e1,1''-diallyl-2'-benzoyl-4'-hydroxy-4'-phenyl-5'-propoxydispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5c)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (76 mg, 79 %); m.p. 166-168 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 0.49 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 1.10 (2H, m), 2.88 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.13 (1H, q , \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), \u0026nbsp; 3.97 (2H, d.d,\u003cem\u003e\u0026nbsp;J\u003c/em\u003e= 15.0 Hz ), 4.21 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 4.51 (2H, d.d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.81 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.16 (1H, quintet, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.22 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 15.0 Hz), 5.28 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 5.75 (1H, quintet, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.04 (1H, \u003cem\u003es\u003c/em\u003e), 6.59 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 6.64 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 6.71 (1H, s), 6.98 -7.24 (13H, m), 7.37 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 7.86 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 8.04 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz) ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 10.7, 22.9, 41.9, 43.2, 58.4, 61.6, 64.5, 73.8, 84.5, 87.9, 100.0, 101.0, 108.8, 109.3, 116.9, 119.0, 122.0, 123.8, 125.9, 126.2, 126.7, 127.3, 127.5, 127.8, 128.7, 129.1, 130.5, 131.5, 131.9, 133.2, 136.8, 137.6, 142.6, 143.7, 176.3, 179.4, 196.6 ppm; Anal. Calcd. for C\u003csub\u003e41\u003c/sub\u003eH\u003csub\u003e38\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e: C, 77.09; H, 6.00; N, 4.39; Found: C, 76.89; H, 6.14; N, 4.21 %\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4'-hydroxy-2'-methyl-4'-phenyl-5'-propoxy-1,1''-dipropyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5d)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (72 mg, 75 %); m.p. 210-212 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 0.49 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 0.55 (3H, t, \u003cem\u003eJ\u003c/em\u003e = 10.0 Hz), 0.93 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 1.00 (2H, m), 1.11 (2H, m), 1.47-1.66 (2H, m), 2.86-3.15 (2H, m ), 3.20-3.38 ( 2H, m), 3.50-3.77 (2H, m), 5.23 (1H, s), 6.03 (1H, s), 6.66 (1H, d, \u003cem\u003eJ\u003c/em\u003e = 10.0 Hz), 6.76 (1H, s), 6.79 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 6.96 (2H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 7.02-7.19 (9H, m), 7.25 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.36 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 7.84 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 8.04 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz) \u0026nbsp;ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 10.7, 11.6, 11.9, 20.4, 21.0, 23.0, 41.3, 42.5, 58.4, 61.5, 64.2, 73.8, 84.6, 87.9, 100.0, 108.2, 109.0, 121.7, 123.6, 125.9, 126.1, 126.6, 127.2, 127.4, 128.6, 129.1, 130.7, 133.1, 136.9, 137.7, 143.1, 144.4, 176.4, 179.6, 196.6 ppm; \u0026nbsp;Anal. Calcd. for C\u003csub\u003e41\u003c/sub\u003eH\u003csub\u003e42\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e: C, 76.61; H, 6.59; N, 4.36; Found: C, 76.43; H, 5.71; N, 4.19\u003c/p\u003e\n\u003cp\u003e2'-benzoyl-1,1''-di(but-2-en-1-yl)-4'-hydroxy-5'-methoxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5e)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (79 mg, 83 %); m.p. 206-208 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 1.41 (3H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz ), 1.65 (3H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 2.93 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.80 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.98 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.19 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.41 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.46 (1H, m), 5.93 (1H, m), 5.26 (1H, \u003cem\u003es\u003c/em\u003e), 5.38 (1H, m), 5.72 (1H, m), 5.94 (1H, \u003cem\u003es\u003c/em\u003e), 6.54-6.67 (3H, m), 6.92 -7.24 (13H, m), 7.36 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 7.84 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 8.04 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz) ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 13.4, 18.0, 36.6, 37.7, 41.0, 42.3, 58.2, 59.8, 61.4, 64.2, 84.5, 89.3, 108.7, 109.4, 121.9, 123.8, 124.2, 124.6, 125.9, 126.1, 126.7, 127.3, 127.5, 127.8, 128.6, 129.1, 129.8, 130.7 133.1, 136.8, 137.6, 142.5, 143.9, 176.1, 179.1, 196.5 ppm; \u0026nbsp;Anal. Calcd. for C\u003csub\u003e41\u003c/sub\u003eH\u003csub\u003e38\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e: C, 77.09; H, 6.00; N, 4.39; Found: C, 76.88; H, 6.08; N, 4.19 %\u003c/p\u003e\n\u003cp\u003e2'-benzoyl-1,1''-di(but-2-en-1-yl)-5'-ethoxy-4'-hydroxy-4'-phenyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dionedione (5f)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (79 mg, 81 %); m.p. 162-164 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ \u0026nbsp;0.72 (3H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 1.41 (3H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz ), 1.64 (3H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 2.95 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.23 \u0026nbsp; (1H, q, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 3.80 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.95 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.19 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.42 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 4.4.67 (1H, m), 4.93 (1H, m), 5.26 (1H, \u003cem\u003es\u003c/em\u003e), 5.39 (1H, m), 5.73 (1H, m), 6.03 (1H, \u003cem\u003es\u003c/em\u003e), 6.56-6.69 (3H, m), 6.94 -7.24 (13H, m), 7.36 (1H, t, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz ), 7.84 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz), 8.02 (1H, d, \u003cem\u003eJ\u003c/em\u003e= 5.0 Hz) ppm; \u003csup\u003e13\u003c/sup\u003eC NMR (176 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 13.5, 15.6, 18.0, 36.6, 37.6, 41.0, 42.2, 58.4, 61.4, 64.2, 67.6, 84.6, 87.8, 108.7, 109.3, 121.9, 123.7, 124.3, 124.6, 125.9, 126.1, 126.5, 126.7, 127.3, 127.5, 127.8, 128.6, 129.1, 129.8, 130.7 133.1, 136.8, 137.6, 142.6, 143.9, 176.1, 179.2, 196.6 ppm; Anal. Calcd. for C\u003csub\u003e42\u003c/sub\u003eH\u003csub\u003e40\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e: C, 77.28; H, 6.18; N, 4.29; Found: C, 77.05; H, 6.32; N, 4.10% .\u003c/p\u003e\n\u003cp\u003e2'-benzoyl-5'-ethoxy-4'-hydroxy-4'-phenyl-1,1''-dimethyldispiro[indoline-3,1'-cyclopentane-3',3''-indoline]-2,2''-dione (5g)\u003c/p\u003e\n\u003cp\u003ewhite solid; yield (70 mg, 85%); m.p. 266-268 °C; \u003csup\u003e1\u003c/sup\u003eH NMR (500 MHz, DMSO-d\u003csub\u003e6\u003c/sub\u003e) δ 0.69 (3H, t,\u0026nbsp;\u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 2.79 (3H, s), 2.96 (1H, q, \u003cem\u003eJ\u003c/em\u003e= 10.0 Hz), 3.11 (3H, s), 3.19 (1H, q, J= 10.0 Hz ), 5.23 (1H, s), 6.02 (1H, s), 6.58 (1H, d, J = 10.0 Hz), 6.75 (2H, d, J = 10.0 Hz), 6.90 -7.13 (10H, m), 7.18 (2H, t, J= 10.0 Hz), 7.26 (1H, t J= 10.0 Hz), 7.35 (1H, t, J= 10.0 Hz), 7.83 (1H, d, J= 5.0 Hz), 8.08(1H, d, J= 5.0 Hz) \u0026nbsp;ppm; 13C NMR (176 MHz, DMSO-d6) δ 15.7, 26.2, 27.1, 58.6, 61.6, 64.6, 67.4, 84.6, 87.4, 108.0, 108.8, 121.9, 123.8, 125.7, 126.0, 126.4, 126.7, 127.2, 127.3, 127.8, 128.4, 129.1, 130.6, 133.1, 136.8, 137.5, 143.3, 144.6, 176.6, 179.7, 196.6 ppm.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully acknowledge the Research Affairs Division Sharif University of Technology (SUT), Islamic Republic of Iran support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eF.M.M. is in charge of overall direction and planning. B.A. devised the project and performed the experiments, analyzed spectra, and wrote the original draft. L.K. performed experiments and wrote the original draft. S.B. performed experiments and wrote the original draft. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplementary information accompanies this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this article [and its supplementary information files]. Crystallographic model data is available through the CCDC under identifier 2327735.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNivetha, N., Patil, S. M., Ramu, R., Sreenivasa, S., \u0026amp; Velmathi, S. Stereoselective Synthesis of Highly Functionalized Aminobenzothiazole-Fused Spirooxindole Derivatives: in silico and in vitro Anti-Diabetic Studies. synth. \u003cstrong\u003e55\u003c/strong\u003e, 4145-4162 (2023).\u003cspan dir=\"RTL\"\u003e\u0026rlm;\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eZhang, J., Li, W. S., Lu, S., Wan, W. J., \u0026amp; Wang, L. X. Highly diastereoselective Mannich reaction between 3‑amino oxindole Schiff base and oxindole ketimines\u0026ndash;Direct and effective preparation of adjacent tetrasubstituted 3, 3\u0026prime;-bisoxindole protected diamines. 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Commun. \u003cstrong\u003e53\u003c/strong\u003e, 1153-1163 (2023).\u003cspan dir=\"RTL\"\u003e\u0026rlm;\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003eAlizadeh, A., \u0026amp; Mokhtari, J. (2011). A Novel, One‐Pot Four‐Component Route to 2\u0026prime;‐Thioxo‐2\u0026prime;, 3\u0026prime;‐dihydrospiro [indole‐3, 6\u0026prime;‐[1, 3] thiazin]‐2‐one Derivatives. Helv. Chim. Acta. \u003cstrong\u003e94\u003c/strong\u003e, 1315-1319 (2011)\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"},{"header":"Schemes","content":"\u003cp\u003eSchemes 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Regio- and diastereoselectivity, kinetically controlled reaction, thioxothiazolidin-indolin-2-ones, dispirocyclopentanebisoxindoles, oxoindolin-carbamodithioate hybrids","lastPublishedDoi":"10.21203/rs.3.rs-4306039/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4306039/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"In this publication, we reported a regio-, diastereoselective, and kinetically controlled reaction for synthesizing thioxothiazolidin-indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles. Obtaining only the kinetic thioxothiazolidin-indolin-2-one products together with their straightforward conversion to dispirocyclopentanebisoxindoles, excellent regio- and diastereoselectivity, easy reaction workup, and one-pot synthetic operation are considerable advantages of this work.\n","manuscriptTitle":"Regio- and diastereoselective synthesis of thioxothiazolidin- indolin-2-ones, oxoindolin-carbamodithioate hybrids, and their base-catalyzed conversion into dispirocyclopentanebisoxindoles","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-15 16:56:10","doi":"10.21203/rs.3.rs-4306039/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-23T07:26:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-23T03:27:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-22T11:49:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-20T07:52:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301979040015726531942876412026400239088","date":"2024-05-15T06:59:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329163664141869847635351844764146006064","date":"2024-05-14T05:56:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"249990425632929489046651376534459617036","date":"2024-05-10T03:35:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"64590878792182158432666861023624981377","date":"2024-05-09T07:47:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-09T05:09:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-09T05:05:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-05-08T22:48:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-08T21:29:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-04-22T12:46:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b59d6575-2f5e-42de-ad3c-d6292863ed6c","owner":[],"postedDate":"May 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":31889571,"name":"Biological sciences/Drug discovery"},{"id":31889572,"name":"Physical sciences/Chemistry"}],"tags":[],"updatedAt":"2024-06-21T15:56:10+00:00","versionOfRecord":{"articleIdentity":"rs-4306039","link":"https://doi.org/10.1038/s41598-024-65087-0","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-06-20 15:56:10","publishedOnDateReadable":"June 20th, 2024"},"versionCreatedAt":"2024-05-15 16:56:10","video":"","vorDoi":"10.1038/s41598-024-65087-0","vorDoiUrl":"https://doi.org/10.1038/s41598-024-65087-0","workflowStages":[]},"version":"v1","identity":"rs-4306039","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4306039","identity":"rs-4306039","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}