The synthesis of the glucuronide metabolite of UK-157,147 using immobilised uridine 5 '-diphosphoglucuronyl transferase and traditional organic chemistry techniques (imidate method)

UK-157,147 (systematic name (3S,4R)-[6-(3-hydroxyphenyl)sulfonyl]-2,2,3-tri methyl-4-(2- methyl-3-oxo-2,3-dihydropyridazin-6-yloxy)-3-chromanol), a pot ent potassium channel opener designed for rapid systemic clearance, is meta bolised in vivo to a glucuronide metabolite. A standard of this metabolite of UK-157,147 was required for biological testing to confirm the absence of pharmacological activity and assay development. The glucuronide conjugate of UK-157,147 was initially synthesised using a bioreactor containing immob ilised microsomes as a source of uridine 5'-diphosphoglucuronyl transferase (E.C.2.4.1.17). At a later date, larger amounts of the glucuronide metabol ite were synthesised by traditional organic chemistry techniques using the imidate method. The identity of the chemically and biocatalytically produce d glucuronide conjugate sample was proven by LC-MS and LC-NMR-MS.