Oguri K, Kuo C K, Yoshimura H
Chem Pharm Bull (Tokyo). 1989 Apr;37(4):955-7. doi: 10.1248/cpb.37.955.
Normorphine-3- and -6-glucuronides were synthesized, and their analgesic effects were examined. Normorphine-3-glucuronide was obtained by condensation of normorphine with acetobromoglucuronate in the presence of sodium hydroxide in acetone. On the other hand, normorphine-6-glucuronide was synthesized by condensing N,O3-biscarbobenzoxynormorphine with acetobromoglucuronate in the presence of silver carbonate, and removing the protecting groups from the resultant reaction product by catalytic hydrogenation and solvolysis with sodium methoxide and barium hydroxide. The analgesic effect of normorphine-6-glucuronide (ED50 0.036 nmol/mice) was 125-fold more potent than that of normorphine in mice injected i.c.v. Normorphine-3-glucuronide was shown to be 37% effective at a dose of 2 nmol/mice, but induced convulsion at higher doses when given by i.c.v. injection.
合成了去甲吗啡 -3- 和 -6- 葡糖苷酸，并检测了它们的镇痛作用。去甲吗啡 -3- 葡糖苷酸是在丙酮中，于氢氧化钠存在的条件下，通过去甲吗啡与乙酰溴葡糖苷酸缩合得到的。另一方面，去甲吗啡 -6- 葡糖苷酸是通过在碳酸银存在的情况下，使 N,O3- 双苄氧羰基去甲吗啡与乙酰溴葡糖苷酸缩合，并通过催化氢化以及用甲醇钠和氢氧化钡进行溶剂分解，从所得反应产物中除去保护基团而合成的。在脑室内注射的小鼠中，去甲吗啡 -6- 葡糖苷酸（半数有效量为 0.036 nmol/ 小鼠）的镇痛作用比去甲吗啡强 125 倍。去甲吗啡 -3- 葡糖苷酸在剂量为 2 nmol/ 小鼠时显示出 37% 的有效性，但通过脑室内注射给予更高剂量时会诱发惊厥。
