Preparative enzymatic synthesis of the acylglucuronide of mycophenolic acid

The acylglucuronide (3) of mycophenolic acid (1) was enzymatically synthesised on a preparative scale (450 mg substrate) under optimised reaction conditions with 51% conversion. By screening 9 liver homogenates from 8 vertebrate species, it was shown that only with liver homogenate from horse as the catalyst were the acyl- (3) and the O-glucuronide (2) were formed in a ca. 1: 1 ratio. With homogenates from other sources, the O-glucuronide (2) was produced in high excess. By optimising the concentration of the co-substrate UDP-glucuronic acid and the reaction temperature, the conversion to the acylglucuronide (3) was increased from initially 34 to 55% and the ratio of acyl- (3) to O-glucuronide (2) from 1.5:1 to 3.9:1. The reaction was also performed continuously in an enzyme membrane reactor, however, with lower conversion yield and therefore, higher specific UDP-glucuronic acid consumption.