Design and synthesis of a potent phorboxazole C(11-15) acetal analogue |
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| Authors: | Smith Amos B Razler Thomas M Meis Regina M Pettit George R |
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| Affiliation: | Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu |
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| Abstract: | [structure: see text] We disclose here the design, synthesis, and biological evaluation of simplified Z- and E-C(2-3) alkynyl phorboxazole C(11-15) acetals (+)-7Z and (+)-7E, wherein the Z-isomer proved to be a potent nanomolar cytotoxic agent. Reevaluation of (+)-C(45-46) E-chloroalkenyl phorboxazole A (6) confirms subnanomolar activity across a broad panel of human cancer cell lines. |
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