Formal Total Synthesis of (±)-Strictamine

Abstract

-A formal total synthesis of an akuammiline-type indole alkaloid, (±)-strictamine, which features ozonolysis, the Staudinger reaction, and the aza-Wittig reaction to construct its D-ring, is reported.

Construction of the Akuammiline Alkaloid Core Structure via Stereoselective E-Ring Formation

“…Akuammilines are a family of monoterpene indole alkaloids that exhibit a broad range of biological activities, including anticancer, antibacterial, anti-inflammatory, antitussive, and antimalarial activities. , Structurally, akuammiline alkaloids feature a highly fused cage-like scaffold with C-ring diversity (shown in blue in Figure ), such as piperidine ( 2 , 3 ), tetrahydrofuran ( 1 , 4 ), or pyrrolidine moieties ( 5 , 6 ). These interesting chemical and biological features have led to several efficient total ,− and formal akuammiline syntheses being reported. Our group recently reported a method for construction of the quaternary carbon center in the akuammiline-type fused indoline moiety via gold­(I)-catalyzed cyclization (Scheme ).…”

Bioinspired Early Divergent Oxidative Cyclizations toward Pleiocarpamine, Talbotine, and Strictamine

“…Pleiocarpamine, strictamine and 17- nor -excelsinidine are representative members of, respectively, the mavacurane, akuammilane, and excelsinidine subfamilies of monoterpene indole alkaloids which are popular targets for total synthesis. , These pentacyclic compounds are constituted of cyclized geissoschizine skeletons via unsolved formal oxidative couplings between the C16-formyl ester and either the C7-indolic carbon for strictamine or the N1-indolic nitrogen for pleiocarpamine or the N4-quinolizidinic nitrogen for 17-nor-excelsinidine (Scheme ).…”