Biogenetically–Sequenced and Concise Total Syntheses of Prenylated and Bicyclo[2.2.2]diazaoctane-containing Indole Alkaloids Including Taichunamide A, Notoamide N and Versicolamide B

Total syntheses of the title prenylated indole alkaloids together with seven others are reported. Biogenetic considerations have been employed in devising the reaction sequences leading to these targets with, in the opening stages, the electrochemically-derived indole-3-carboxaldehyde 15 being subject to an aldol-type condensation reaction involving the diketopiperazine derivative 19. This led, after prototopic shifts, intramolecular Diels-Alder (IMDA) cycloaddition and hydrolysis/deprotection steps, to the racemic forms of the bicyclo[2.2.2]diazaoctane-containing natural product stephacidin A (2) and its C6-epimer 3. Epoxidation of the last compound afforded, following rearrangement of the primary oxidation product, a mixture of (±)-taichunamide A [(±)-4] and (±)-versicolamide B [(±)-7]. Related protocols allowed for the conversion of (±)-stephacidin A [(±)-2] into (±)-notoamide B [(±)-5]. Analogous aldol-condensation, nucleophilic reduction and epoxidation steps allowed for the formation of (–)-notoamide E and its conversion into notoamide C as well as the indole fragmentation product amoenamide E. A late-stage nuclear chlorination reaction applied to (±)-stephacidin A provided access to the spirocyclic oxindole (±)-notoamide N.