Acid-catalyzed reactions of homohalichondrin B, a marine sponge-derived antitumor polyether macrolide
Acid-catalyzed reactions of homohalichondrin B, a marine sponge-derived antitumor polyether macrolide
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DOI：
10.1021/jo951877x
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发表时间：
1996-04-19
影响因子：
3.6
通讯作者：
Munro, MHG
中科院分区：
文献类型：
--
作者：
Hart, JB;Blunt, JW;Munro, MHG
软海绵素是一系列海洋海绵衍生的聚醚大环内酯类化合物，具有显著的抗肿瘤活性。1-6软海绵素B（1）已被美国国家癌症研究所（NCI）选为临床前开发药物，作为针对选定人类癌细胞的有效药物。7国家癌症研究所这种状况的直接后果是迫切需要这种稀有化合物的充足供应。这可以从自然资源或可能的合成来解决。软海绵素家族的酸稳定性的知识是必不可少的任何大规模的分离，构效关系的研究，并合成这一系列。这已经是我们的经验，以及其他人的经验，2，8软海绵素对暴露于酸性条件敏感，例如可以存在于用于NMR光谱实验的CDCl 3中。我们现在报告在各种酸性条件下的软海绵素的行为的系统研究。
The halichondrins are a series of marine spongederived polyether macrolide compounds with a remarkable antitumor potency. 1-6 Halichondrin B (1) has been selected by the NCI (USA) for preclinical development as an effective agent against selected human cancer cells. 7 An immediate consequence of this status at the NCI is the pressing need for adequate supplies of this rare compound. This can be addressed from natural resources, or possibly synthesis. A knowledge of the acid stability of the halichondrin family is essential for any large-scale isolation, structure-activity studies on, and synthesis of this series. It has already been our experience, and that of others, 2, 8 that the halichondrins are sensitive to exposure to acid conditions, such as can exist in the CDCl3 used for NMR spectroscopy experiments. We now report on a systematic study of the behavior of the halichondrins under a variety of acidic conditions.