从链霉菌属中分离得到的2',5'-磷酸二酯酶抑制剂A-74528的结构解析

Structural elucidation of A-74528, an inhibitor for 2',5'-phosphodiesterase isolated from Streptomyces sp.

作者信息

Fujita Yoko, Kasuya Atsushi, Matsushita Yoichi, Suga Miwa, Kizuka Masaaki, Iijima Yasuteru, Ogita Takeshi

机构信息

Sankyo R&D Facility, Sankyo Co. Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan.

出版信息

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4317-21. doi: 10.1016/j.bmcl.2005.06.047.

DOI:10.1016/j.bmcl.2005.06.047

PMID:16061376

Abstract

A-74528 (1) is a metabolite of Streptomyces sp. discovered in the screening for 2',5'-oligoadenylate phosphodiesterase inhibitors. The planar structure of 1 was mainly elucidated by NMR techniques including natural abundance INADEQUATE, and the relative configuration and the conformation were elucidated by the analyses of NOEs and assessment of dihedral angles predicted by QUANTA/CHARMm computations and coupling constants. It was proved that 1 is a highly fused polyketide with a side-chain branching site that never appeared before from the nature.

摘要

A-74528 (1) 是链霉菌属的一种代谢产物，是在筛选2',5'-寡腺苷酸磷酸二酯酶抑制剂的过程中发现的。化合物1的平面结构主要通过包括天然丰度INADEQUATE在内的核磁共振技术得以阐明，其相对构型和构象则通过对核Overhauser效应（NOE）的分析以及对由QUANTA/CHARMm计算预测的二面角和耦合常数的评估来确定。已证实化合物1是一种高度稠合的聚酮化合物，带有一个自然界中从未出现过的侧链分支位点。