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Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation.

ABSTRACT: A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling ?-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed moderate to good cytotoxicity.

SUBMITTER: Zhao J

PROVIDER: S-EPMC3225578 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation.

Zhao Jielu J Bane Susan S Snyder James P JP Hu Haipeng H Mukherjee Kamalika K Slebodnick Carla C Kingston David G I DG

Bioorganic & medicinal chemistry 20111013 24

A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling β-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed mod ...[more]

PMID: 22071526

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