Synthesis of paclitaxel-C3′-14C

Reductive cleavage of the C13 side chain of paclitaxel (3) followed by regioselective silylation gave 7-triethylsilylbaccatin III (6). Successive reaction of L-threonine methyl ester hydrochloride (7) with tert-butoxydiphenylchlorosilane, benzaldehyde-C7- 14 C and acetoxyacetyl chloride/triethylamine gave a 92:8 ratio (NMR) of azetidinones 10:11 in 57% yield from 7. Removal of the chiral auxiliary led to 16, which after 3-O-triethylsilylation and N-benzoylation provided (3R,4S)-cis-1-benzoyl-3-O-(triethylsilyl)-4-phenylazetidin-2-one-C4- 14 C (18). Coupling of 18 and 6 followed by deprotection gave 1.12 g of paclitaxel-C3'- 14 C (2) having a specific activity of 16.4 mCi/mmol and a radiochemical purity of 96%