Study on Preparation Technology of 10-Acetoacetylpaclitaxel Standard

OBJECTIVE To study the synthesis of 10-acetoacetylpaclitaxel, one of impurities from semi-synthetic paclitaxel. METHODS Paclitaxel was reacted with silicon reagent to selectively protect the C2' and C7 hydroxyl group, then C10 acetyl group was hydrolyzed using alkaline and unprotected C10 hydroxyl group was reacted with 2,2,6-trimethyl-4H-1,3-dioxin-4-one. At last, the target compound 10-acetoacetylpaclitaxel was prepared by deprotection of silicon group. RESULTS 10-acetoacetylpaclitaxel was prepared by a 5-step reaction using paclitaxel as the start material, the overall yield was 27% and the purity was up to 95%. CONCLUSION Provided a simple and convenient method for the preparation of 10-acetoacetylpaclitaxel, and it is helpful for quality control and evaluation of semi-synthetic paclitaxel.