半佛波唑A：结构确证、类似物设计及生物学评价。
Hemi-phorboxazole a: structure confirmation, analogue design and biological evaluation.
作者信息
Smith Amos B, Liu Zhuqing, Hogan Anne-Marie L, Dalisay Doralyn S, Molinski Tadeusz F
机构信息
Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
出版信息
Org Lett. 2009 Aug 20;11(16):3766-9. doi: 10.1021/ol9014317.
Abstract
A synthesis providing totally synthetic (+)-hemi-phorboxazole A (1), proceeding in two steps (85% yield) from known vinyl iodide precursor (+)-2, has been achieved in conjunction with the design, synthesis, and biological evaluation of two hemi-phorboxazole analogues [(+)-3 and (-)-4] featuring ring replacements inscribed within the macrolide. Although hemi-phorboxazole A (1) displayed no activity when tested against Candida albicans and two human cancer cell lines, analogue (-)-4 exhibited significant tumor cell growth inhibitory activity in the nanomolar range against HCT-116 (colon) and SK-BR-3 (breast), while (+)-3 displayed promising antifungal activity against C. albicans.
摘要
已实现了一种全合成（+）-半佛波唑A（1）的方法，该方法从已知的乙烯基碘前体（+）-2分两步进行（产率85%），同时还进行了两种半佛波唑类似物[（+）-3和（-）-4]的设计、合成及生物学评估，这两种类似物在大环内酯内具有环取代特征。尽管半佛波唑A（1）在针对白色念珠菌和两种人类癌细胞系进行测试时未显示活性，但类似物（-）-4在纳摩尔范围内对HCT-116（结肠）和SK-BR-3（乳腺）表现出显著的肿瘤细胞生长抑制活性，而（+）-3对白色念珠菌显示出有前景的抗真菌活性。
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