抗肿瘤药。278. 从西加罗林群岛的一种海洋海绵中分离出轴海绵他汀2和3并确定其结构。

Antineoplastic agents. 278. Isolation and structure of axinastatins 2 and 3 from a western Caroline Island marine sponge.

作者信息

Pettit G R, Gao F, Cerny R L, Doubek D L, Tackett L P, Schmidt J M, Chapuis J C

机构信息

Cancer Research Institute, Arizona State University, Tempe 85287-1604.

出版信息

J Med Chem. 1994 Apr 15;37(8):1165-8. doi: 10.1021/jm00034a014.

DOI:10.1021/jm00034a014

PMID:8164258

Abstract

The Republic of Palau marine sponge Axinella sp. was found to be an exceptionally productive source of cell growth inhibitory substances. The strongly antineoplastic polyether macrocyclic lactones halichondrin B (1) and homohalichondrin B (2) were isolated in 1.2 x 10(-6)% and 5.4 x 10(-7)% yields, respectively. In addition to axinastatin 1 (3), two new and cytostatic (GI50 values of 0.35 to 0.0072 microgram/mL against six human cancer cell lines) cycloheptapeptides designated axinastatins 2 (4) and 3 (5) were discovered in 1.4 x 10(-6)% and 1.25 x 10(-6)% yields. Structures were elucidated by high-resolution FABMS and tandem MS/MS techniques augmented by high-field (400 and 500 MHz) 2D-NMR spectral analyses. The absolute configurations were established by a combination of hydrolysis, derivatization, and chiral gas chromatographic methods.

摘要

帕劳共和国的海洋海绵Axinella sp.被发现是细胞生长抑制物质的一个极为丰富的来源。强抗肿瘤聚醚大环内酯类化合物halichondrin B（1）和高halichondrin B（2）的分离产率分别为1.2×10⁻⁶%和5.4×10⁻⁷%。除了轴抑素1（3）之外，还发现了两种新的具有细胞抑制作用（对六种人类癌细胞系的GI50值为0.35至0.0072微克/毫升）的环庚肽，分别命名为轴抑素2（4）和轴抑素3（5），产率分别为1.4×10⁻⁶%和1.25×10⁻⁶%。通过高分辨率FABMS和串联MS/MS技术，并辅以高场（400和500 MHz）二维NMR光谱分析来阐明其结构。通过水解、衍生化和手性气相色谱方法相结合确定了绝对构型。