Studies on the Synthesis of Phlegmarine-Type Lycopodium Alkaloids: Enantioselective Synthesis of (−)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline

The synthesis of the Lycopodium alkaloids, (−)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between (R)- or (S)-phenylglycinol and the substituted δ-keto ester 11, easily accessible from (R)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the (S)-2-(piperidyl)­methyl moiety and the stereoselective removal of the chiral inductor to give a cis-decahydroquinoline.

本研究报道了以苯甘氨醇衍生的三环内酰胺（phenylglycinol-derived tricyclic lactams）作为手性骨架，合成石松生物碱（Lycopodium alkaloids）类化合物(−)-西米齐宁B ((−)-cermizine B)、(+)-锯齿齐明E ((+)-serratezomine E)与(+)-光泽定 ((+)-luciduline)的方法。所需内酰胺可通过(R)-或(S)-苯甘氨醇与取代δ-酮酯11的环缩合反应制备，该取代δ-酮酯11可由(R)-胡薄荷酮（(R)-pulegone）便捷获得。本研究探讨了调控此类环缩合反应立体选择性的关键因素。从立体化学视角来看，该合成路线的核心步骤包括：将烯丙基取代基立体选择性修饰为(S)-2-(哌啶基)甲基基团，以及立体选择性脱除手性诱导剂以得到顺式十氢喹啉（cis-decahydroquinoline）。