A synthesis of morphine-6-glucuronide

doi:10.1016/0040-4039(95)00649-W

Tetrahedron Letters

Volume 36, Issue 22, 29 May 1995, Pages 3949-3950

https://doi.org/10.1016/0040-4039(95)00649-W Get rights and content

Abstract

A practical synthesis of morphine-6-glucuronide from 3-acetylmorphine and methyl 2-α-bromo-3,4,5-tri-O-acetylglucuronate is described. Similar syntheses of codeine-6-glucuronide, codeine-6-glucoside and morphine-6-glucoside are also documented

Graphic

References (8)

R.T. Brown et al.
Tetrahedron Letters
(1995)
G. Schneider et al.
Tetrahedron
(1989)
Y.D. Vankar et al.
Tetrahedron
(1991)
R. Osborne et al.
Br. J. Clin. Pharm.
(1992)

There are more references available in the full text version of this article.

Cited by (16)

New approach in the synthesis of M6G
2011, Tetrahedron Letters
Citation Excerpt :
So, treatment of morphine with various acid chlorides furnished dimers in acceptable to good yields (Table 1). The best results were obtained with terephthaloyl chloride which led to the target compound 2a18 in 92% yield. Structure of compounds 2a–k was confirmed by NMR spectroscopy.19
Morphine-6-glucuronide (M6G) is the primarily active metabolite of morphine, produced endogenously by the UGT enzyme, which displays analgesic activity. For this reason, M6G is a promising drug candidate for the treatment of severe pain. We described herein a new, efficient and scalable synthesis of M6G using dimorphinic derivatives. This preparation of M6G could be performed on multigram scale with good yield and high purity.
Use of O-glycosylation in total synthesis
2005, Tetrahedron
Selective synthesis of both isomers of morphine 6-β-D-glucuronide and their analogs
2001, Tetrahedron
A stereoselective synthesis of both isomers of the pharmaceutically important morphine 6-β-d-glucuronide (M6G) and its analogs was developed. The method is based on the use of ZnBr₂ for the key coupling reaction. It was shown that the α/β stereoselectivity of the reaction can be directed and controlled by the amount of ZnBr₂. This paper describes the synthesis, analysis and characterization of the α-isomer of M6G, useful as a reference marker for testing purity and stability of the morphine 6-β-d-glucuronide (M6G).
Synthesis of morphine 6-α-D-glucuronide
2000, Tetrahedron Letters
This paper provides the first report on stereoselective synthesis and characterization of morphine 6-α-d-glucuronide (M6αG), useful as a reference marker for testing the purity and stability of the pharmaceutically important morphine 6-β-d-glucuronide (M6G). The synthesis is based on the glycosylation of 3-O-acetylated morphine with methyl 2,3,4-tri-O-acetyl-d-glucopyranosyluronate bromide as glycosyl donor and zinc bromide as catalyst. Furthermore, we showed that the α/β stereoselectivity of the reaction can be directed and controlled by the amount of zinc bromide.
The enzymatic glucuronidation of 3-O-protected morphine - A new route to 7,8-dihydromorphine-6-glucuronide
2000, Tetrahedron Asymmetry
The selective enzymatic glucuronidation of the 6-position of morphine was probed by the glucuronidation of a series of 3-O-protected morphine derivatives. 3-O-Benzylmorphine 5 was converted to the corresponding 3-O-benzylmorphine-6-glucuronide 8 by human liver microsomes. The identity of 8 was confirmed by independent chemical synthesis. The glucuronide 8 was subsequently converted to 7,8-dihydromorphine-6-glucuronide.
Synthesis of a morphine-6-glucuronide hapten, N-(4-aminobutyl)normorphine-6-glucuronide, and related haptens
1995, Tetrahedron Letters

View all citing articles on Scopus

View full text

A synthesis of morphine-6-glucuronide

Abstract

Tetrahedron Letters

Tetrahedron

Tetrahedron

Br. J. Clin. Pharm.