Phorboxazole Synthetic Studies: Design, Synthesis and Biological Evaluation of Phorboxazole A and Hemi-Phorboxazole A Related Analogues

Overview

Journal Tetrahedron

Specialty Chemistry

Date 2011 Aug 4

PMID 21811346

Citations 2

Authors

Amos B Smith 3rd

Anne-Marie L Hogan

Zhuqing Liu

Thomas M Razler

Regina M Meis

Brandon I Morinaka

Tadeusz F Molinski

Affiliations

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Abstract

The design, synthesis and biological evaluation of a new phorboxazole analogue, comprising an acetal replacement for the C-ring tetrahdropyran of the natural product and carrying a potency-enhancing C(45-46) vinyl chloride side chain, is described. In addition, the synthesis of (+)-hemi-phorboxazole A and a series of related hemi-phorboxazole A analogues has been achieved. The new acetal ring replacement analogue displayed activity comparable to that of the parent natural product against HCT-116 (colon) cells (IC(50) 2.25 ng/mL). Equally important, the phorboxazole analogue and two related hemiphorboxazole A congeners exhibited significant antifungal activity when assayed against pathogenic Candida albicans strains.

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