Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9, Budapest, Hungary.
Eur J Pharm Sci. 2011 Jan 18;42(1-2):65-72. doi: 10.1016/j.ejps.2010.10.007. Epub 2010 Oct 27.
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.
16 个吗啡、可待因及其一些 N-甲基季铵衍生物的 3-O-和 6-O-硫酸盐酯通过吡啶-SO3 复合物和硫酸/N，N'-二环己基碳二亚胺的磺化作用合成。根据一维和二维同核和异核测量，给出了每个合成化合物的完整的（1）H 和（13）C-NMR 分配。通过圆二色性和旋光色散分析比较手性性质，发现由于电荷、极性和分子内氢键引起的水合溶液中内在相互作用的变化，光谱中存在特征差异。合成的硫酸盐酯是潜在的外周镇痛药，缺乏中枢副作用，也可用作涉及硫酸盐酯代谢物的各种分析研究的参比物质。
