Barber R B, Rapoport H
J Med Chem. 1975 Nov;18(11):1074-7. doi: 10.1021/jm00245a006.
A practical synthesis of thebaine and oripavine has been developed from codeine and morphine, respectively. Attempts to use a codeinone intermediate gave poor yields; however, methylation of the potassium salt of codeine to give codeine methyl ether followed by oxidation with gamma-MnO2 gave thebaine in 67% yield from codeine. Similarly, the potassium salt of the di-O-anion of morphine was selectively alkylated to give morphine 6-methyl ether (heterocodeine) in better than 90% yield. Hetercodeine was then acetylated and oxidized to oripavine 3-acetate which was hydrolyzed to give oripavine in 73% yield from morphine.
分别从可待因和吗啡出发，已开发出一种实用的蒂巴因和阿片托品合成方法。尝试使用酮可待因中间体时产率较低；然而，将可待因的钾盐甲基化得到可待因甲醚，然后用γ - 二氧化锰氧化，可待因制得蒂巴因的产率为67%。同样，吗啡的二 - O - 阴离子钾盐经选择性烷基化，以高于90%的产率得到吗啡6 - 甲醚（异可待因）。然后将异可待因乙酰化并氧化得到阿片托品3 - 乙酸酯，将其水解，由吗啡制得阿片托品的产率为73%。
