A novel route for the preparation of betamethasone from 9 alpha-hydroxyandrost-4-ene-3,17-dione (9 alpha OH-AD) by chemical synthesis and fermentation

作者：Tang, Jie; Liu, Xirong; Zeng, Chunlin; Meng, Hao; Tian, Mi; Guo, Cancheng^*

来源：Journal of Chemical Research, 2017, 41(5): 266-270.

DOI：10.3184/174751917X14925986241025

• betamethasone
• phytosterol
• 9 alpha OH-AD
• fermentation

A novel and efficient synthesis of betamethasone has been developed from the readily available 9 alpha-hydroxyandrost-4-ene-3,17-dione (9 alpha OH-AD). The 16 alpha-methyl was introduced stereoselectively with CH3Br and converted to the 16 beta-methyl, the 17-side chain was installed with 2-chlorovinyl ethyl ether in the place of the toxic KCN/HOAc, and a mild fermentation was employed for the 1,2-dehydrogenation, replacing the DDQ oxidation. By adjustments and improvements of the steps, this route produced betamethasone in 11 steps with a 22.9% overall yield, showing its potential for industrial application with relatively low toxicity and cost.

• 出版日期2017-5
• 单位湖南大学