合成、结构测定和破坏素 E 的生物评价。

Synthesis, structure determination, and biological evaluation of destruxin E.

机构信息

Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.

出版信息

Org Lett. 2010 Sep 3;12(17):3792-5. doi: 10.1021/ol101449x.

PMID:20672849

Abstract

The total synthesis of destruxin E (1) has been achieved for the first time, and the stereochemistry of its chiral center at the epoxide has been determined to be (S). The cyclization precursor 3a was synthesized by solid-phase peptide synthesis. Macrolactonization of 3a utilizing MNBA-DMAPO, followed by formation of the epoxide, then furnished destruxin E. Its diastereomer, epi-destruxin E (2), was also synthesized in the same manner. Furthermore, the biological evaluation indicated that destruxin E exhibits V-ATPase inhibitory activity 10-fold greater than that of epi-destruxin E.

摘要

首次实现了 destruxin E（1）的全合成，并确定了其环氧手性中心的立体化学为（S）。通过固相肽合成合成了环化前体 3a。利用 MNBA-DMAPO 进行 3a 的大环内酯化，然后形成环氧，最终得到 destruxin E。其非对映异构体，epi-destruxin E（2）也以相同的方式合成。此外，生物评价表明 destruxin E 对 V-ATPase 的抑制活性比 epi-destruxin E 强 10 倍。