Sulfate esters of morphine derivatives: Synthesis and characterization

被引：15

作者：

Andras Varadi ^{[1
]}

Andras Gergely ^{[1
]}

Szabolcs Beni ^{[1
]}

Peter Jankovics ^{[2
]}

Bela Noszal ^{[1
]}

Sandor Hosztafi ^{[1
]}

机构：

[1] Semmelweis Univ, Dept Pharmaceut Chem, H-1092 Budapest, Hungary

[2] Natl Inst Pharm, H-1051 Budapest, Hungary

来源：

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | 2011年 / 42卷 / 1-2期

关键词：

Morphine; Sulfate ester; NMR; CD; ORD; CIRCULAR-DICHROISM SPECTRA; CHEMICAL SYNTHESIS; OPIUM-ALKALOIDS; METABOLITES; RATS; MORPHINE-6-SULFATE; 6-GLUCURONIDE; ANTAGONISTS; EXPRESSION; PRODRUGS;

D O I：

10.1016/j.ejps.2010.10.007

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Sixteen 3-O- and 6-O-sulfate esters of morphine, codeine and some of their N-methyl quaternary derivatives were synthesized by means of sulfation with pyridine-SO(3) complex and sulfuric acid/N,N'-dicyclohexylcarbodiimide. Complete (1)H- and (13)C-NMR assignments are given for each of the synthesized compounds based on one- and two-dimensional homo- and heteronuclear measurements. Comparative analysis of chiral properties by circular dichroism and optical rotatory dispersion revealed characteristic differences in the spectra due to changes in charge, polarity and intramolecular association by strong hydrogen bonds in aqueous solution. The synthesized sulfate esters are prospective peripheral analgesics lacking central side effects and are also useful as reference substances for various analytical studies involving sulfate ester metabolites. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：65 / 72

页数：8

共 34 条

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Chemical sulfation of small molecules-advances and challenges [J].