Synthesis of a novel C-10 spiro-epoxide of paclitaxel.
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).
Walker
M A
MA
Bristol-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
Johnson
T D
TD
Huang
S
S
Vyas
D M
DM
Kadow
J F
JF
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004852:Epoxy Compounds; D017239:Paclitaxel