Total Synthesis of (±)-Maistemonine, (±)-Stemonamide, and (±)-Isomaistemonine

A full account of the total synthesis of (±)-maistemonine,
(±)-stemonamide, and (±)-isomaistemonine is presented. Two
approaches have been developed to construct the basic pyrrolo­[1,2-a]­azepine core of the Stemona alkaloids,
featuring a tandem semipinacol/Schmidt rearrangement of a secondary
azide and a highly stereoselectively desymmetrizing intramolecular
Schmidt reaction, respectively. To build the common spiro-γ-butyrolactone,
a new protocol was carried out by utilizing an intramolecular ketone-ester
condensation as the key transformation. The vicinal butyrolactone
moiety of (±)-maistemonine was stereoselectively introduced via
a one-pot procedure involving the epimerization at C-3 and carbonyl
allylation/lactonization. Moreover, (±)-stemonamide was divergently
synthesized from a common intermediate, and (±)-isomaistemonine
was obtained via the epimerization of (±)-maistemonine at C-12.

本文完整报道了(±)-马藤次碱（(±)-maistemonine）、(±)-百部酰胺（(±)-stemonamide）以及(±)-异马藤次碱（(±)-isomaistemonine）的全合成研究。本研究开发了两种策略构建百部生物碱（Stemona alkaloids）的核心母核吡咯并[1,2-a]氮杂卓（pyrrolo[1,2-a]azepine），分别以二级叠氮化物的串联半频哪醇/施密特重排反应，以及高立体选择性去对称化分子内施密特反应为关键步骤。为构建共用的螺环-γ-丁内酯（spiro-γ-butyrolactone）结构单元，本研究开发了全新的合成策略，以分子内酮-酯缩合反应作为关键转化步骤。(±)-马藤次碱的邻位丁内酯结构单元通过一锅法实现了高立体选择性构建，该方法包含C-3位差向异构化以及羰基烯丙基化/内酯化串联反应。此外，(±)-百部酰胺可通过共用中间体实现发散式合成，而(±)-异马藤次碱则通过(±)-马藤次碱的C-12位差向异构化得到。