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Published on: February 7, 2019
Synthesis of a novel C-10 spiro-epoxide of paclitaxel
M A Walker1, T D Johnson, S Huang
1Bristol-Myers Squibb, Pharmaceutical Research Institute, Richard L. Gelb Center for Pharmaceutical Research and Development, 5 Research Parkway, 06492, Wallingford, CT, USA. michael.a.walker@bms.com
Abstract:
New analogues of paclitaxel (1a, active constituent of Taxol) were synthesized containing an epoxide at the C-10 position. The introduction of the epoxide was carried out by selective removal of the C10-acetate followed by protection of the C2'- and C7-hydroxyl groups. After oxidation to yield a ketone at the C10-position, this intermediate was reacted with dimethylsulfonium ylide. Deprotection and further manipulations provide the C10-spiro epoxide of paclitaxel (1b) and the corresponding C7-MOM ether (1c).
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