从海洋来源真菌喙突曲霉中产生的具有细胞毒性的二硫化物——喙菌素A-D的分离与结构鉴定

Isolation and structure assignments of rostratins A-D, cytotoxic disulfides produced by the marine-derived fungus Exserohilum rostratum.

作者信息

Tan Ren Xiang, Jensen Paul R, Williams Philip G, Fenical William

机构信息

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California 92093-0204, USA.

出版信息

J Nat Prod. 2004 Aug;67(8):1374-82. doi: 10.1021/np049920b.

DOI:10.1021/np049920b

PMID:15332857

Abstract

Four new cytotoxic disulfides, rostratins A-D (1-4), were isolated from the whole broth of the marine-derived fungus Exserohilum rostratum (Drechsler), a fungal strain found associated with a marine cyanobacterial mat. The structures of these cyclic dipeptides were established through chemical degradation and a variety of two-dimensional NMR techniques. The absolute configurations of the rostratins were determined by the modified Mosher method. In the case of the polyhydroxylated compound 1 and the mercaptol 4, regioselective acylation was achieved by modulating the reaction temperature while monitoring the progress of the reaction by 1H NMR. Rostratins A, B, C, and D showed in vitro cytotoxicity against human colon carcinoma (HCT-116) with IC50 values of 8.5, 1.9, 0.76, and 16.5 microg/mL, respectively.

摘要

从海洋来源的真菌喙孢（德雷克斯勒）的全发酵液中分离出四种新的细胞毒性二硫化物，即喙孢菌素A-D（1-4），该真菌菌株与海洋蓝藻垫有关。这些环二肽的结构通过化学降解和各种二维核磁共振技术确定。喙孢菌素的绝对构型通过改良的莫舍尔方法确定。对于多羟基化化合物1和巯基化合物4，通过调节反应温度并通过1H NMR监测反应进程实现了区域选择性酰化。喙孢菌素A、B、C和D对人结肠癌（HCT-116）显示出体外细胞毒性，IC50值分别为8.5、1.9、0.76和16.5μg/mL。