Division of Organic Chemistry, National Chemical Laboratory (CSIR) , Pune 411 008, India.
J Org Chem. 2017 Oct 20;82(20):11126-11133. doi: 10.1021/acs.joc.7b02122. Epub 2017 Oct 4.
A facile synthesis of (±)-subincanadine E was described from tryptamine-based maleimide. 1,2-Addition of Grignard reagent to maleimide, internal activation of formed lactamol for in situ 1,4-addition of Grignard reagent, and associated position-specific allylic rearrangement in diastereoselective Pictet-Spengler cyclization were the key steps. Enantioselective first total synthesis of naturally occurring cytotoxic (+)-subincanadine E was also accomplished from (S)-acetoxysuccinimide via an unusual syn-addition of cuprate to the α,β-unsaturated lactam. Sinister absolute configuration was assigned to (+)-subincanadine E on the basis of total synthesis. (S)-Acetoxy group in the succinimide precursor was initially employed to impart regio- and stereoselectivity and then as a suitable leaving group to generate the desired conjugated lactam.
从色胺衍生的马来酰亚胺出发，描述了（±）-次南美藤碱 E 的简便合成方法。格氏试剂与马来酰亚胺的 1,2-加成、形成的内酰胺醇的原位 1,4-加成、以及在非对映选择性 Pictet-Spengler 环化中的相关位置特异性烯丙基重排是关键步骤。通过（S）-乙酰氧基琥珀酰亚胺的非寻常顺式加成到α,β-不饱和内酰胺，也完成了天然存在的细胞毒性（+）-次南美藤碱 E 的首次对映选择性全合成。根据全合成，（+）-次南美藤碱 E 的绝对构型被指定为辛立体构型。在脯氨酸前体中的（S）-乙酰氧基基团最初被用来赋予区域和立体选择性，然后作为合适的离去基团来生成所需的共轭内酰胺。
