irciniastatin A 及其 C1-C2 炔烃类似物的合成与生物评价。

Syntheses and biological evaluation of irciniastatin A and the C1-C2 alkyne analogue.

机构信息

Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan.

出版信息

Org Lett. 2010 Mar 5;12(5):1040-3. doi: 10.1021/ol1000389.

DOI:10.1021/ol1000389

PMID:20141170

Abstract

Syntheses of both natural (+)- and unnatural (-)-irciniastatin A (aka psymberin) as well as a C1-C2 alkyne analogue of (+)-irciniastatin A have been achieved. The key features of the syntheses include a highly regioselective epoxide-opening reaction and a late-stage assembly of C1-C6, C8-C16, and C17-C25 fragments. (+)-Alkymberin retained a high level of cytotoxicity, whereas (-)-irciniastatin A showed almost no activity. These results suggest that (+)-alkymberin could be a useful enantio-differential probe for mode-of-action study.

摘要

天然 (+)-和非天然 (-)-irciniastatin A（又名 psymberin）以及 (+)-irciniastatin A 的 C1-C2 炔烃类似物的合成已经完成。这些合成的关键特点包括高度区域选择性的环氧化物开环反应以及 C1-C6、C8-C16 和 C17-C25 片段的晚期组装。(+)-alkymberin 保留了高水平的细胞毒性，而 (-)-irciniastatin A 几乎没有活性。这些结果表明 (+)-alkymberin 可能是一种有用的对映体差异探针，可用于作用模式研究。