An efficient protocol for synthesis of hydroxamic acids via methane sulphonic anhydrides: An in-silico ADME properties of the synthesised amino acid derivative of hydroxamic acids | 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 Research Article An efficient protocol for synthesis of hydroxamic acids via methane sulphonic anhydrides: An in-silico ADME properties of the synthesised amino acid derivative of hydroxamic acids Krishnaiah Cheruvupalli, Venkata Ratnam Kesamsetty, Nagaraju Kerru, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8232113/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Jan, 2026 Read the published version in International Journal of Peptide Research and Therapeutics → Version 1 posted 7 You are reading this latest preprint version Abstract A simple, cost-effective, metal-free, and high-yielding protocol has been described for the development of hydroxamic acid scaffolds from N - α -protected amino acids and aryl carboxylic acids. This method employs economical reagents, methanesulfonic anhydride and Hunig’s base (DIPEA) and is carried out via a telescoped process. The approach offers several advantages, including the use of inexpensive reagents, high product yields, easy removal of by-products such as methanesulfonic acid, unreacted protected amino acids/aryl carboxylic acids, and DIPEA, and the ability to produce high-purity products. Moreover, the method demonstrates compatibility with various protecting groups, viz ., Boc, Fmoc, and Cbz. The efficiency of the optimized procedure was validated by applying it to a range of protected amino acids and aryl carboxylic acids, consistently delivering excellent yields and purity. Additionally, the biological potential of the synthesized hydroxamic acid derivatives was assessed through in-silico ADME profiling and molecular docking investigations accomplished against E. coli DNA Gyrase B and CYP51. This enables us to evaluate the interactions of the synthesized compounds with enzyme active sites, and the findings are discussed in detail. Nα-protected hydroxamic acids Methane Sulphonic anhydride One-pot Hydroxyl amine hydrochloride Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 17 Jan, 2026 Read the published version in International Journal of Peptide Research and Therapeutics → Version 1 posted Editorial decision: Revision requested 13 Dec, 2025 Reviews received at journal 13 Dec, 2025 Reviewers agreed at journal 04 Dec, 2025 Reviewers invited by journal 04 Dec, 2025 Editor assigned by journal 30 Nov, 2025 Submission checks completed at journal 30 Nov, 2025 First submitted to journal 28 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8232113","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":555519781,"identity":"7f5cb2bf-424d-49a8-b7bc-f1328374eaa4","order_by":0,"name":"Krishnaiah Cheruvupalli","email":"","orcid":"","institution":"GITAM Deemed to be University","correspondingAuthor":false,"prefix":"","firstName":"Krishnaiah","middleName":"","lastName":"Cheruvupalli","suffix":""},{"id":555519782,"identity":"e3d62fe9-0e2b-466c-93e7-e4e96811946a","order_by":1,"name":"Venkata Ratnam Kesamsetty","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYDACHijNz8DYAGEdIFaLZANjYwNpWgwOwKwhpMXgzOHDH37m1MkZn1/c/uBnDoMc340EAlrOtqVJ9m47bGx242FjY+82BmNJQlok+3nMGHi3HUjcduNgYwPvNobEDYS18H/++HdbXf3mGQcbG/9uY6gnqIWft4dBmncbc4IBf2NjM9CWBAOCWniOmUnLbjtsOOMGY+Ns2W0ShjPPPMCvhY0n+fHHt9vq5Pn7jz8AMmzk+Y4TsAUBJMAqJYhVDnbiAVJUj4JRMApGwUgCADhNTEnYkak3AAAAAElFTkSuQmCC","orcid":"","institution":"GITAM Deemed to be University","correspondingAuthor":true,"prefix":"","firstName":"Venkata","middleName":"Ratnam","lastName":"Kesamsetty","suffix":""},{"id":555519784,"identity":"22a8556c-e0b5-4354-bde0-c78694c7255f","order_by":2,"name":"Nagaraju Kerru","email":"","orcid":"","institution":"GITAM Deemed to be University","correspondingAuthor":false,"prefix":"","firstName":"Nagaraju","middleName":"","lastName":"Kerru","suffix":""},{"id":555519786,"identity":"17893acf-9ce4-4b09-a65e-a84eaab51fc4","order_by":3,"name":"Ch. 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