Mechanism of Acyl Migration in an Acyl Glucuronide and Formation of a Lysyl Adduct of a Drug

This shows an acyl migration reaction in an acyl glucuronide conjugate of a drug, R. The acyl migration is separate from the adduct formation and doesn't "lead" to it in any specific way, but the acyl migrations can cause the glucuronide conjugates to be poorer substrate of enzymes that exhibit glucuronidase activity (tissue-specific esterase enzymes, mainly, are the enzymes that the beta-2-O-acyl-glucuronide and beta-3 and beta-4 conjugates are poor substrates of), in the intestinal tract or in "extraintestinal" cells. Those positional isomers of the beta-1-O-acyl glucuronides can (just as the beta-1 isomer can) also allow the drug and the glucuronic acid moiety to be linked to the protein covalently, and that can impact the immunogenicity, etc. (I didn't show that example).