Decoration of the Aromatic Ring of Dihydrocodeinone (Hydrocodone) and 14-Hydroxydihydrocodeinone (Oxycodone)

Improved protocols for the preparation of 1-bromodihydrocodeinone (1-bromohydrocodone) and 1-bromo-14-hydroxydihydrocodeinone (1-bromooxycodone) and synthesis of the
corresponding 1-chloro and 1-iodo derivatives have been
achieved using the corresponding N-halosuccinimides in
acidic milieu. The corresponding 1-carboethoxy derivative
of 14-hydroxydihydrocodeinone (1-carboethoxyoxycodone)
has been prepared by Pd-catalyzed reaction with carbon
monoxide in ethanol. The ester was hydrolyzed to the
corresponding zwitterionic amino acid.

本研究以相应的N-卤代琥珀酰亚胺（N-halosuccinimides）为反应试剂，在酸性环境中优化了1-溴二氢可待因酮（1-bromodihydrocodeinone，别名1-溴氢可酮）与1-溴-14-羟基二氢可待因酮（1-bromo-14-hydroxydihydrocodeinone，别名1-溴羟考酮）的制备工艺，并成功合成了二者对应的1-氯代与1-碘代衍生物。通过钯催化下一氧化碳与乙醇的反应，制备得到14-羟基二氢可待因酮对应的1-乙氧羰基衍生物（1-carboethoxyoxycodone，别名1-乙氧羰基羟考酮）。将该酯类化合物水解，得到对应的两性离子氨基酸。