Synthesis and biological evaluation of phorboxazole congeners leading to the discovery and preparative-scale synthesis of (+)-chlorophorboxazole a possessing picomolar human solid tumor cell growth inhibitory activity

The Journal of Organic Chemistry
Amos B SmithGeorge R Pettit

Abstract

Highly convergent syntheses of eight phorboxazole congeners and their evaluation against a diverse panel of human solid tumor cancer cell lines have been achieved. Specifically, the C(45-46) alkyne, alkene, and alkane phorboxazole A analogues [(+)-4-(+)-6] were constructed and found to display single digit nanomolar cell growth inhibitory activities in a series of human cancer cell lines. The structurally simplified C(11-15)-acetal congener (+)-20Z also proved potent albeit reduced (cf. 34.6 nM) when evaluated against the same cell line panel. Importantly, (+)-C(46)-chlorophorboxazole A (3) displayed picomolar (pM) inhibitory activity in several cell lines.

References

May 17, 2001·Bioorganic & Medicinal Chemistry Letters·F M Uckun, C J Forsyth
Aug 12, 2004·Journal of the American Chemical Society·Ramesh JastiScott D Rychnovsky
Aug 28, 2004·Organic Letters·Brian S LucasSteven D Burke
Oct 14, 2004·Organic & Biomolecular Chemistry·Ian PatersonChris A Luckhurst
Feb 14, 2006·Organic Letters·Amos B SmithGeorge R Pettit
Mar 23, 2006·Journal of the American Chemical Society·Craig J ForsythJames J La Clair

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Citations

Jul 30, 2009·Organic Letters·Amos B SmithTadeusz F Molinski
Dec 9, 2010·Marine Drugs·Danilo Davyt, Gloria Serra
Apr 8, 2011·Natural Product Reports·Zhong Jin
Jan 25, 2008·The Journal of Organic Chemistry·Amos B SmithRegina M Meis
Apr 4, 2009·Organic Letters·Doralyn S Dalisay, Tadeusz F Molinski
Apr 28, 2009·The Journal of Organic Chemistry·Jie ChenXiao-Ping Cao
Dec 31, 2010·Journal of the American Chemical Society·Bo WangCraig J Forsyth
Dec 31, 2010·Journal of the American Chemical Society·Bo WangCraig J Forsyth

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