title: Phorboxazole Synthetic Studies: Design, Synthesis and Biological Evaluation of Phorboxazole A and Hemi-Phorboxazole A Related Analogues.
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.
authors.affiliation: Department of Chemistry, Laboratory for Research on the Structure of Matter and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
authors.forename: Anne-Marie L
authors.initials: AM
authors.lastname: Hogan
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Liu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Razler
authors.forename: Regina M
authors.initials: RM
authors.lastname: Meis
authors.forename: Brandon I
authors.initials: BI
authors.lastname: Morinaka
authors.forename: Tadeusz F
authors.initials: TF
authors.lastname: Molinski