TY - JOUR
T1 - Chemical and enzyme-assisted syntheses of norbuprenorphine-3-β-D- glucuronide
AU - Fan, Jinda
AU - Brown, Sarah M.
AU - Tu, Zhude
AU - Kharasch, Evan D.
PY - 2011/4/20
Y1 - 2011/4/20
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=79955010401&partnerID=8YFLogxK
U2 - 10.1021/bc100550u
DO - 10.1021/bc100550u
M3 - Article
C2 - 21434652
AN - SCOPUS:79955010401
SN - 1043-1802
VL - 22
SP - 752
EP - 758
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 4
ER -