Semisynthesis and biological activity of taxol analogues: baccatin III 13-(N-benzoyl-(2′R,3′S)-3′-(p-tolyl)isoserinate), baccatin III 13-(N-(p-toluoyl)-2′R,3′S)-3′-phenylisoserinate), baccatin III 13-(N-benzoyl-(2′R,3′S)-3′-(p-trifluoromethylphenyl)isoserinate), and baccatin III 13-(N-(p-trifluoromethylbenzoyl)-(2′R,3′S)-3′-phenylisoserinate)

Abstract

The semisynthesis of the four novel taxol analogues baccatin III 13-(N-benzoyl-(2'R,3'S)-3'-(p-tolyl)isoserinate) (2), baccatin III 13-(N-p-toluoyl)-(2'R,3'S)-3'-phenylisoserinate) (3), baccatin III 13-(N-benzoyl-(2'R,3'S)-3'-(p-trifluoromethylphenyl)isoserinate) (4), and baccatin III 13-(N-(p-trifluoromethylbenzoyl)-(2'R,3'S)-3'-phenylisoserinate) (5) from 7-triethylsilyl baccatin III (6) and the N-acyl-3-ethoxyethyl-β-azetidinones (11-14) is described. Derivatives 2,3, and 5 demonstrated activity comparable to taxol (1) in the microtubule assembly assay and cytotoxicity against B16 melanoma cells. Derivative 4, however, was found to be an unstable product.