Synthesis of a novel C-10 spiro-epoxide of paclitaxel.

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 ).