放线菌产生的萜类化合物：新二萜，吉福诺酮 A 和 B 的分离、结构阐明和生物合成来自格尔福斯孢菌 YM28-088。

Terpenoids produced by actinomycetes: isolation, structural elucidation and biosynthesis of new diterpenes, gifhornenolones A and B from Verrucosispora gifhornensis YM28-088.

机构信息

Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.

出版信息

J Antibiot (Tokyo). 2010 May;63(5):245-50. doi: 10.1038/ja.2010.30. Epub 2010 Apr 9.

DOI:10.1038/ja.2010.30

PMID:20379218

Abstract

New terpenoids named gifhornenolones A (1) and B (2) were isolated from the culture broth of Verrucosispora gifhornensis YM28-088, and their structures were established as hydroxylated isopimaradiene derivatives on the basis of extensive NMR and MS spectral analyses. In addition, a known sesquiterpene compound cyperusol C (3) was isolated. The absolute configuration of 1 was determined by nuclear Overhauser effect spectroscopy (NOESY) and CD spectra as 4R, 5S, 9R, 10S, 13R, and that of 2 was determined by NOESY experiments as 3R, 4R, 5R, 9R, 10S, 13R. Labeling experiments with [1-(13)C]glucose and [U-(13)C(6)]glucose confirmed that the MEP (2-C-methyl-D-erythritol-4-phosphate) pathway was used for the biosynthesis of terpenoids in this organism. 1 showed potent inhibitory activity to the androgen receptor with an IC(50) of 2.8 microg ml(-1).

摘要

新型萜类化合物被命名为 gifhornenolones A（1）和 B（2），从 Verrucosispora gifhornensis YM28-088 的发酵液中分离得到，其结构基于广泛的 NMR 和 MS 光谱分析确定为羟基化异戊二烯衍生物。此外，还分离出一种已知的倍半萜化合物 cyperusol C（3）。通过核Overhauser 效应光谱（NOESY）和 CD 光谱确定 1 的绝对构型为 4R,5S,9R,10S,13R，通过 NOESY 实验确定 2 的绝对构型为 3R,4R,5R,9R,10S,13R。用 [1-(13)C]葡萄糖和 [U-(13)C(6)]葡萄糖进行标记实验证实，该生物中萜类化合物的生物合成途径是 MEP（2-C-甲基-D-赤藓醇-4-磷酸）途径。1 对雄激素受体具有很强的抑制活性，IC(50)为 2.8 µg ml(-1)。