Smith Amos B, Liu Zhuqing, Hogan Anne-Marie L, Dalisay Doralyn S, Molinski Tadeusz F
Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Org Lett. 2009 Aug 20;11(16):3766-9. doi: 10.1021/ol9014317.
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.
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。