Lipase-catalyzed synthesis of (S)-naproxen ester prodrug by transesterification in organic solvents.
A lipase-catalyzed enantioselective transesterification process was developed for the synthesis of (S)-naproxen 2-N-morpholinoethyl ester prodrug from racemic 2,2,2-trifluoroethyl naproxen ester in organic solvents. By selecting isooctane and 37 degrees C as the best solvent and temperature, the apparent fits of the initial conversion rates for transesterification and hydrolysis side reaction suggest a ping-pong Bi-Bi enzymatic mechanism with the alcohol as a competitive enzyme inhibitor. Improvements in the initial conversion rate and the productivity for the desired (S)-ester product were obtained after comparing with the result of an enantioselective esterification process. Studies of water content in isooctane and alcohol containing various N,N-dialkylamino groups on the enzyme activity and enantioselectivity, as well as the recovery of (S)-ester product by using extraction, were also reported.
Tsai
S W
SW
Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan, Republic of China. t62647@mail.ncku.edu.tw
Tsai
C S
CS
Chang
C S
CS
D000438:Alcohols / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004951:Esterification; D004952:Esters; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D009288:Naproxen / Q000138:chemical synthesis* / Q000737:chemistry; D009930:Organic Chemicals; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013696:Temperature; D014867:Water / Q000737:chemistry
D000438:Alcohols; D004952:Esters; D009930:Organic Chemicals; D011355:Prodrugs; D012997:Solvents; D014867:Water; D009288:Naproxen; D008049:Lipase