替曲诺丁，一种由链霉菌属NR0489产生的新型胆囊收缩素B型受体拮抗剂。III. 结构解析。

Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. III. Structural elucidation.

作者信息

Ohtsuka T, Nakayama N, Itezono Y, Shimma N, Kuwahara T, Yokose K, Seto H

机构信息

Nippon Roche Research Center, Kamakura, Japan.

出版信息

J Antibiot (Tokyo). 1993 Jan;46(1):18-24. doi: 10.7164/antibiotics.46.18.

DOI:10.7164/antibiotics.46.18

PMID:8436552

Abstract

Tetronothiodin (1) is a potent and selective cholecystokinin type B (CCK-B) receptor antagonist produced by Streptomyces sp. NR0489. Its structure was elucidated to be a macrocyclic compound comprising cyclohexene, alpha-acyltetronic acid and tetrahydrothiophene moieties based on various 2D NMR experiments on 1 and its dihydro derivative. The stereochemistries for the cyclohexene and tetrahydrothiophene rings were elucidated based on the analysis of NOEs obtained by NOESY experiments and NOE difference spectroscopy. The relative configuration of the cyclohexene moiety in 1 was revealed to be the same as that of the corresponding part in kijanimicin and chlorothricin, which can be structurally related to 1 in terms of their containing a cyclohexene ring with a spirotetronic acid in the molecule.

摘要

替曲硫定（1）是由链霉菌属NR0489产生的一种强效且具选择性的胆囊收缩素B型（CCK - B）受体拮抗剂。基于对1及其二氢衍生物进行的各种二维核磁共振实验，其结构被阐明为一种包含环己烯、α - 酰基特窗酸和四氢噻吩部分的大环化合物。通过NOESY实验和NOE差值光谱分析得到的NOE，阐明了环己烯和四氢噻吩环的立体化学结构。1中环己烯部分的相对构型被揭示与基贾尼霉素和氯丝菌素中相应部分的相对构型相同，就它们在分子中含有一个带有螺特窗酸的环己烯环而言，它们在结构上与1相关。