Enantioselective synthesis of saframycin A and evaluation of antitumor activity relative to ecteinascidin/saframycin hybrids.
Enantioselective synthesis of saframycin A and evaluation of antitumor activity relative to ecteinascidin/saframycin hybrids.
复制标题
DOI：
10.1021/ol990553i
复制
发表时间：
1999-05
期刊：
影响因子：
5.2
通讯作者：
E. Martinez;E. Corey
中科院分区：
文献类型：
--
作者：
E. Martinez;E. Corey
[公式：描述了一种沙夫霉素A的简短合成方法，该方法从以前用于海鞘素743的全合成的容易获得的中间体开始。该合成中的关键步骤是使用1-氟-3，5-二氯吡啶鎓三氟甲磺酸盐将酚环氧化成1，4-苯醌单元，同时将不同酚环的甲氧基甲基醚裂解成相应的苯酚（4->5）。用于合成沙夫拉霉素A（1）和海鞘素743的共同中间体（2）也允许合成这些结构的两种杂合物（6和7）。使用肺、结肠、黑色素瘤和前列腺来源的肿瘤细胞系进行的抗肿瘤活性的全细胞生物测定允许在该系列中结构与生物活性的明确相关性。
[formula: see text] A short synthesis of saframycin A is described which begins with a readily available intermediate previously utilized for the total synthesis of ecteinascidin 743. A key step in this synthesis is the use of 1-fluoro-3,5-dichloropyridinium triflate to oxidize a phenolic ring to a 1,4-benzoquinone unit while simultaneously cleaving a methoxymethyl ether of a different phenolic ring to the corresponding phenol (4-->5). The common intermediate (2) for the synthesis of saframycin A (1) and ecteinascidin 743 also allowed the synthesis of two hybrids of these structures (6 and 7). Whole cell bioassays for antitumor activity using lung, colon, melanoma, and prostate-derived tumor cell lines allowed a clear correlation of structure with biological activity in this series.