（+）-盘状海绵内酯的全合成：利用带有C1-C8β-酮膦酸酯片段的斯蒂尔-根纳里型烯烃化反应改进的最后一步。

Total synthesis of (+)-discodermolide: an improved endgame exploiting a Still-Gennari-type olefination with a C1-C8 beta-ketophosphonate fragment.

作者信息

Paterson Ian, Lyothier Isabelle

机构信息

University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.

出版信息

Org Lett. 2004 Dec 23;6(26):4933-6. doi: 10.1021/ol0478842.

DOI:10.1021/ol0478842

PMID:15606103

Abstract

[structure: see text] An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 10:1 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.

摘要

[结构：见正文] 实现了海洋海绵来源的强效微管稳定抗癌剂（+）-discodermolide的改进的第三代全合成，21步反应的产率为11.1%。关键步骤包括在C1-C8β-酮膦酸酯7和C9-C24醛8之间使用NaH作为碱进行的Still-Gennari HWE烯化反应，以10:1的选择性引入（8Z）-烯烃，以及对所得烯酮16进行K-Selectride还原反应，引入（7S）-构型。