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Published on: July 18, 2012
Hemi-phorboxazole a: structure confirmation, analogue design and biological evaluation
Amos B Smith1, Zhuqing Liu, Anne-Marie L Hogan
1Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
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.
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