Cella J A, Kelley J A
J Pharm Sci. 1977 Jul;66(7):1054-6. doi: 10.1002/jps.2600660744.
The preparation of 6-spin-labeled codeine and morphine is described. Treatment of either 6-chlorocodide or 8-bromocodide with 4-amino-2,2,6,6-tetramethylpiperidino-1-oxyl free radical in dimethylformamide afforded 6-spin-labeled codeine. Similar treatment of 6-chloromorphide afforded 6-spin-labeled morphine. Exclusive formation of the 6-isomer in these reactions is explained by halide-ion-catalyzed isomerization of the 6-halo opiate to the 8-halo isomer followed by a normal SN2' displacement of the halogen. Both spin-labeled compounds displayed weak in vivo analgesic activity and did not bind appreciably to receptors in brain homogenate.
描述了6-自旋标记可待因和吗啡的制备方法。在二甲基甲酰胺中，用4-氨基-2,2,6,6-四甲基哌啶-1-氧基自由基处理6-氯可待因或8-溴可待因，得到6-自旋标记可待因。对6-氯吗啡进行类似处理，得到6-自旋标记吗啡。这些反应中6-异构体的专一形成是由6-卤代阿片向8-卤代异构体的卤离子催化异构化，随后卤素进行正常的SN2'取代来解释的。两种自旋标记化合物在体内均表现出较弱的镇痛活性，且在脑匀浆中与受体的结合不明显。
