Chemical and Enzyme-Assisted Syntheses of Norbuprenorphine-3-尾-d-glucuronide

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• 作者：Jinda Fan ; Sarah M. Brown ; Zhude Tu ; Evan D. Kharasch
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：April 20, 2011
• 年：2011
• 卷：22
• 期：4
• 页码：752-758
• 全文大小：856K
• 年卷期：v.22,no.4(April 20, 2011)
• ISSN：1520-4812

文摘

Norbuprenorphine-3-尾-d-glucuronide (nBPN-3-尾-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 ¹H 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.