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.

distilled and the residue was chromatographed as described for the preparation above, yielding 0.110 g (0.45 mmol) of 4, 0.417 g (2.24 mmol) of 3, and 1.796 g (9.54 mmol) of 2.C. Uv Irradiation.•-A homogeneous solution of 1.35 g (7.33 mmol) of S4N4, 200 ml of benzene, and 4.15 g (31.39 mmol) of tetrahydronaphthalene was irradiated for 206 hr at room temperature. After removal of the solvent under vacuum at room temperature, the residue was chromatographed. In addition to the unreacted tetrahydronaphthalene, 0.256 g (1.36 mmol) of 2 and 0.067 g (0.36 mmol) of 3 were obtained. Compound 4 was recovered in traces and identified by tic analysis.Reaction of S4N4 with 2.-A 0.748-g (3.97 mmol) sample of 2 in 20 ml of xylene was treated with 1.10 g (5.97 mmol) of S4N4 and the mixture was refluxed for about 8 hr under nitrogen atmosphere with stirring. After removal of the solvent by distillation at 20 Torr, the residue was chromatographed, yielding 0.059 g (0.24 mmol) of 4, 0.229 g (1.23 mmol) of 3, and 0.469 g (2.49 mmol) of 2.Reaction of 2 with Sulfur.-A mixture of 0.109 g (0.58 mmol) of 2 and 0.022 g (0.69 mmol) of sulfur was heated at 250-270°f or 2.5 hr. After cooling the residue gave after crystallization from methanol 0.078 g (0.42 mmol) of 3.

Three isomeric hemigossypol derivatives (3,4,5) have been synthesized. Two of these derivatives (3,4) and one synthetic intermediate (7) have been shown to have activity comparable to gossypol (1) in a sperm motility assay.

Production of luteoskyrin, a hepatotoxin synthesized by Penicillium islandicum Sopp., was studied with various fermentation methods. Best results were obtained in static fermentations on glutinous rice at 30 degrees C. The isolated yield of pure luteoskyrin was approximately 400 mg per kg of rice. Also produced were skyrin, islandicin, iridoskyrin, rubroskyrin, chrysophanol, mannitol, and erythritol. A new metabolite, which we call pibasterol, was also isolated.