Integrated Chemistry Engine, Eisai AiM Institute , 4 Corporate Drive, Andover, Massachusetts 01810, United States.
Org Lett. 2017 Nov 17;19(22):6092-6095. doi: 10.1021/acs.orglett.7b02934. Epub 2017 Oct 27.
Prins reaction of homoallenyl alcohols with aldehyde dimethylacetals in the presence of methoxyacetic acid directly affords tetrasubstituted pyrans relevant to halichondrins with complete control of the C27 stereogenic center. Regioselective Tsuji reduction of the resultant allylic acetates stereoselectively establishes the C25 stereogenic center and C26 exocyclic olefin. Building upon these findings, we achieved concise access to the halichondrin C14-C38 and eribulin C14-C35 fragments.
在手性偕二烯醇与醛二甲缩醛在甲氧基乙酸存在下的普林斯反应中，直接得到与卤虫内酯相关的完全控制 C27 立体中心的四取代吡喃。所得烯丙基醋酸盐的区域选择性 Tsuji 还原立体选择性地建立 C25 立体中心和 C26 环外烯烃。基于这些发现，我们实现了简洁地获得卤虫内酯 C14-C38 和埃博霉素 C14-C35 片段的方法。
