99043-04-6Relevant academic research and scientific papers
Effective synthesis of 1β-acyl glucuronides by selective acylation
Perrie, Jennifer A.,Harding, John R.,Holt, David W.,Johnston, Atholl,Meath, Paul,Stachulski, Andrew V.
, p. 2591 - 2594 (2005)
(Chemical Equation Presented) Acyl glucuronides are vital metabolites for many carboxylic acid containing drugs. We report an efficient new method for the chemical synthesis of these molecules by selective 1β-acylation of allyl glucuronate with carboxylic
Convenient syntheses of the in vivo carbohydrate metabolites of mycophenolic acid: reactivity of the acyl glucuronide
Jones, Amy E.,Wilson, Helen K.,Meath, Paul,Meng, Xiaoli,Holt, David W.,Johnston, Atholl,Oellerich, Michael,Armstrong, Victor W.,Stachulski, Andrew V.
supporting information; experimental part, p. 4973 - 4977 (2009/12/05)
Following in vivo use of mycophenolic acid, the O-aryl and O-acyl glucuronides, as well as the recently discovered O-aryl glucoside (Scheme 1), are all found as metabolites. We describe convenient preparations of all three derivatives. The phenolic glycos
Efficient synthesis of 1β-O-acyl glucuronides via selective acylation of allyl or benzyl d-glucuronate
Bowkett, Elizabeth R.,Harding, John R.,Maggs, James L.,Park, B. Kevin,Perrie, Jennifer A.,Stachulski, Andrew V.
, p. 7596 - 7605 (2008/02/08)
Acyl glucuronides are key metabolites for many carboxylic acid-containing drugs, notably those of the non-steroidal anti-inflammatory class. In the processes of drug safety assessment and new drug development, it is essential that acyl glucuronides, if formed in vivo, should be made conveniently available for bioevaluation. We recently showed that selective acylation of allyl glucuronate is a promising method for the synthesis of these metabolites in good yield and with excellent β-anomeric selectivity. We now give fuller details of the allyl ester method and further report that benzyl glucuronate performs at least equally well in the acylation step, offering the advantage of very mild deprotection by catalytic transfer (or conventional) hydrogenation. Depending on the compatibility of other functional groups, as discussed below, this will be the method of choice for many acyl glucuronide syntheses. The value of the method is demonstrated in particular by the synthesis of several acyl glucuronides that are known metabolites of important drugs.
Preparative Enzymatic Synthesis of the Acylglucuronide of Mycophenolic Acid
Kittelmann, Matthias,Rheinegger, Urs,Espigat, Aude,Oberer, Lukas,Aichholz, Reiner,Francotte, Eric,Ghisalba, Oreste
, p. 825 - 829 (2007/10/03)
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.
