title: Chemical and enzyme-assisted syntheses of norbuprenorphine-3-β-D-glucuronide.
abstract: Norbuprenorphine-3-β-d-glucuronide (nBPN-3-β-d-G, 1) is a major phase II metabolite of buprenorphine, a pharmaceutical used for the treatment of opioid addiction. The pharmacological activity of compound 1 is not clear because investigations have been limited by the lack of chemically pure, well characterized 1 in sufficient quantities for in vitro and in vivo experiments. This work describes two concise, new methods of synthesis of 1, a chemical and an enzyme-assisted synthesis. The chemical synthesis used a strategy based on a combination of Koenig-Knorr coupling and amino-silyl protection. The enzyme-assisted synthesis used dog liver to convert the substrate norbuprenorphine (nBPN, 2) to 1. Both methods provided 1, characterized by (1)H NMR and tandem mass spectrometry, with purity >96%. The fractional yield of the enzyme-assisted synthesis was greater than that of the chemical synthesis (67% vs 5.3%), but due to larger reaction volumes, the chemical synthesis afforded greater amounts of total 1.
authors: Department of Radiology, Washington University in St. Louis, 660 S. Euclid Avenue, St. Louis, Missouri 63110, United States.
authors: Jinda
authors: J
authors: Fan
authors: Sarah M
authors: SM
authors: Brown
authors: Zhude
authors: Z
authors: Tu
authors: Evan D
authors: ED
authors: Kharasch
mesh_terms: D000818:Animals; D055162:Biocatalysis; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004285:Dogs; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: C499393:norbuprenorphine-3-beta-D-glucuronide; D002047:Buprenorphine; C043585:norbuprenorphine; D005954:Glucosephosphate Dehydrogenase