(-)-4-Hydroxymorphinanones: their synthesis and analgesic activity.

A facile procedure is described for the conversion of morphine, via the diphosphate ester derivative 1 followed by catalytic reduction and treatment with Li/NH3, to 3-deoxy-7,8-dihydromorphine (3). Oxidation with benzophenone tert-butoxide converted 3 to the ketone 4, which on treatment with Zn/NH4Cl formed (-)-4-hydroxymorphinan-6-one 5. Reaction of 5 with diazomethane formed the methyl ether 6. The N-cyclopropylmethyl analogues of 4 and 5 were also prepared, i.e., 8c and 9 from 4. The antinociceptive activity of these compounds was tested. Compounds 5, 6, 8c, and 9 showed potent antiwrithing activity and, based on these data, a structure-activity relationship in morphinans is discussed.