首次全合成管碟菌素 B。

First total synthesis of tubulysin B.

机构信息

Leibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany.

出版信息

Org Lett. 2009 Dec 17;11(24):5567-9. doi: 10.1021/ol902320w.

DOI:10.1021/ol902320w

PMID:19919080

Abstract

The first total synthesis of tubulysin B is described. The aziridine route to tubuphenylalanine (Tup) of the tubulysin D/U-series could not be transferred to the synthesis of tubutyrosine (blue moiety). Therefore, tubutyrosine (Tut) was synthesized by a Wittig olefination/diastereoselective catalytic reduction sequence. Interestingly, the C-2 epimer of tubulysin B has a cytotoxic activity almost identical to the natural diastereomer.

摘要

本文描述了tubulysin B 的首次全合成。tubulysin D/U 系列中环丁烷氨基酸（Tup）的氮杂环丙烷路线无法转化为tubutyrosine（蓝色部分）的合成。因此，采用Wittig 烯烃化/非对映选择性催化还原序列合成了tubutyrosine（Tut）。有趣的是，tubulysin B 的 C-2 差向异构体的细胞毒性活性几乎与天然非对映异构体相同。