Synthesis and analgesic effect of normorphine-3- and -6-glucuronides

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.