A two-step, high yield, method for synthesizing naturally derived, Hemi-Phorboxazole A analogs
Problem:
(+)-Phorboxazole A and B, extracted from the sponge Phorbas sp., display extraordinary anti-proliferative activity against National Cancer Institute’s (NCI) panel of 60 human tumor cell lines. Due to their complex structures, the reported syntheses of Phorboxazole A and B analogues consist of 100 total steps with an average yield of 4%. The limited availability of these compounds has precluded the evaluation of their biological activity. As such, there is a need for improved syntheses of these compounds, featuring fewer steps while providing higher yield and selectivity.
Solution:
Researchers in the Smith Lab have developed a two-step, high yield (85%) method for preparing Hemi-Phorboxazole A from a known precursor. Two analogues of Hemi-Phorboxazole were designed and synthesized in this manner. One analogue exhibits anti-proliferation activities of human cancer cell lines HCT-116 (colon) and SPKB-3 (breast). Another analogue shows antifungal activity against Candida albicans.
Advantages:
- Efficient two-step method to synthesize complex and scarce molecules, compared to previously-reported syntheses having 100 steps
- Improved synthetic yield (~85%) over other reported procedures (average 4%)
- Less expensive process than other known procedures
Applications:
- Antitumor activities for colon and breast cancer cell lines
- Antifungal activity against Candida albicans
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Synthesis of completely synthetic (+)-hemi-phorboxazole A. From Smith AB et al, 2009.
Stage of Development:
In vitro testing in human cell lines
Intellectual Property:
Reference Media:
- Smith AB et al. Org. Lett., 2009, 11(16), p. 3766-3769.
- Dalisay DS et al. Org. Lett., 2009, 11(9), p. 1967-1970.
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