Phorboxazole synthetic studies: design, synthesis and biological evaluation of phorboxazole A and hemi-phorboxazole A related analogues

The design, synthesis and biological evaluation of a new phorboxazole analogue, comprising an acetal replacement for the C-ring tetrahydropyran 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 (IC50 2.25 ng/mL). Equally important, the phorboxazole analogue and two related hemi-phorboxazole A congeners exhibited significant antifungal activity when assayed against pathogenic Candida albicans strains.