Abstract：
Codeine N-oxide 2 is an active metabolite of codeine obtained by oxidation and observed as a degradant in codeine drug products such as syrups. Oxidation of codeine\'s N-methyl function can deliver two regio-isomers due to chirality of the tetra-substituted nitrogen. Hydrogen peroxide oxidation of codeine was performed and induced two different isomers in a 9:1 ratio; these isomers were isolated using preparative high performance liquid chromatography (HPLC) and fully characterized by nuclear magnetic resonance (NMR) techniques. We describe the complete assignment of the minor isomer of codeine N-oxide 3 and attribute a (S) configuration (N-methyl axial) of the tetra-substituted nitrogen. The effects of N-oxidation on the 15 N chemical shifts of the codeine are presented. The 15 N shifts were determined using the CIGAR-HMBC experiment at natural abundance, and the nitrogen resonance of codeine shifted downfield from 42.8 to 118.7 ppm for both N-oxide isomers.
摘要：
可待因N-氧化物2是通过氧化获得的可待因的活性代谢物,并且在可待因药物产品如糖浆中被观察为降解物。由于四取代氮的手性,可待因的N-甲基官能团的氧化可产生两种区域异构体。进行可待因的过氧化氢氧化，并以9：1的比例诱导两种不同的异构体；使用制备型高效液相色谱（HPLC）分离这些异构体，并通过核磁共振（NMR）技术充分表征。我们描述了可待因N-氧化物3的次要异构体的完全分配，并归因于四取代氮的（S）构型（N-甲基轴向）。介绍了N氧化对可待因15N化学位移的影响。使用CIGAR-HMBC实验在自然丰度下确定了15个N偏移，对于两种N-氧化物异构体，可待因的氮共振从42.8降至118.7ppm。
