Synthesis of Water-soluble Paclitaxel Derivatives

2'-O-[4-N, N-dimethylamino-2(R)-fluoro-butyryl]-paclitaxel hydrochloride(VI) was synthesized via esterification, condensation, selective deprotection using Bakatin III (I) as raw material. The esterification between 7-O-benzyloxycarbonyl-paclitaxel (IV) and (R)-4-N, N-dimethylamino-2-fluoro-butyryl chloride hydrochloride (VII) led to 2'-O-[4-N, N-dimethylamino-2(R)-fluoro-butyryl]-7-O-benzyloxycarbonyl-paclitaxel hydrochloride (V).Compound VI was obtained by the hydrogenolysis of compound V. The effects of volume ratio of trifluoroacetic acid and acetic acid on reaction time during the preparation of compound IV, dosage of (R)-4-N, N-dimethylamino-2-fluoro-butanoic acid hydrochloride (VIII), and dosage of catalyst 4-DMAP on the conversion rate of compound VI during the preparation of compound V were investigated. The optimal conditions were as following: V(trifluoroacetic acid): V(acetic acid)=1: 8, n(IV): n(4-DMAP): n(VIII)=1: 3: 3. The structure of target product was confirmed by MS, 1HNMR and 13CNMR. The synthesis process in this study was simple, and the overall yield was more than 60%.In addition, the purity of compound VI reached 99%(HPLC). © 2017, Editorial Office of FINE CHEMICALS. All right reserved.