Preparative Enzymatic Synthesis of the Acylglucuronide of Mycophenolic Acid

✍ Scribed by Matthias Kittelmann; Urs Rheinegger; Aude Espigat; Lukas Oberer; Reiner Aichholz; Eric Francotte; Oreste Ghisalba

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 86 KB
• Volume: 345
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/adsc.200303044

✦ Synopsis

Abstract

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.