Highly efficient synthesis of 5′− O−palmitoyl−5−fluorouridine catalyzed by Lipozyme TL IM

ORGN 715

Xue-dan Hou, xuedan_hou@126.com1, Min-Hua Zong, btmhzong@scut.edu.cn2, Hong Wu, bbhwu@scut.edu.cn2, and Wen-Yong Lou, wylou@scut.edu.cn2. (1) School of Biological Science and Engineering, South China University of Technology, Guangzhou, KS 510640, China, (2) Laboratory of Applied Biocatalysis, South China University of Technology, Guangzhou, 510640, China
5′−O−Palmitoyl−fluorouridine (5′ −O−palmitoyl−5−FUR), a promising anti−tumor drug, was efficiently synthesized by Lipozyme TL IM−mediated regioselective acylation of 5−FUR with vinyl palmitate in acetone−THF (85/15, v/v) co−solvent mixture. The molar ratio of vinyl palmitate to 5−FUR could be substantially lowered (from 15 to 2) by limiting the hydrolysis of vinyl palmitate via controlling water in the reaction system with molecular sieves while keeping excellent yield and regioselectivity of the reaction. Under the optimal conditions, the yield in a 10 ml and a 200 ml batch system reached 98.6% and 99.0%, respectively with regioselectivity being both as high as 99%. In addition, Lipozyme TL IM displayed a good operational stability and 96.3% of its original activity was maintained after being reused for 10 cycles. Moreover, the productivity of the enzymatic reaction was significantly improved by using the packed bed reactor instead of the batch one (39.0 g/L• h vs 1.2 g/L•h)