Chemical and enzyme-assisted syntheses of norbuprenorphine-3-β-D-glucuronide.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Fan, J; Brown, SM; Tu, Z; Kharasch, ED

Published Date

  • April 20, 2011

Published In

Volume / Issue

  • 22 / 4

Start / End Page

  • 752 - 758

PubMed ID

  • 21434652

Pubmed Central ID

  • PMC3091394

Electronic International Standard Serial Number (EISSN)

  • 1520-4812

Digital Object Identifier (DOI)

  • 10.1021/bc100550u

Language

  • eng

Conference Location

  • United States