マトリン誘導体の合成 (第1報)

Abstract

In order to prepare the derivative of decarbonylmethylmatrinamine, its acylation was attempted by the application of tosyl chloride, 4-nitrobenzoyl chloride, and 3, 4-dinitrobenzoyl chloride, but acylated compounds could not be obtained in a crystalline state. Application of acetic anhydride yielded a monoacetate of needles, m. p. 123.5-124°, and the application of α-chlorocinchonic chloride gave the acid amide of needles, m.p. 162-164°. Application of sodium butoxide to the acid amide resulted in the formation of α-butoxycinchonic acid decarbonylmethylmatrinamide, which possesses a structure similar to Nupercaine but failed to show any striking local anesthetic action.Reduction of methyl methylmatrinate with lithium aluminum hydride gives the corresponding primary alcohol, i.e. methylmatrine alcohol as prisms of m.p. 82-83°, [α]D12: -35.52°, which gives a monomethiodide of needles, m.p. 177-178°, and a phenylurethane of prisms, m.p. 269-272°. Treatment of this methylmatrine alcohol with thionyl chloride in chloroform yields the corresponding chloride which, in a free state, transits to the quaternary ammonium chloride. This quaternary salt was found to be identical with matridine methochloride from which it was realized that the quaternary nitrogen in matridine methiodide is the tertiary amine-nitrogen that was newly formed by the reduction of the lactim ring in matrine. Boiling of methylmatrine alcohol with diphen-ylmethyl bromide in toluene results in the formation of a corresponding diphenylmethyl ether of prisms, m.p. 68-70°, which gives a monomethiodide of needles, m.p. 185-186°, picrate of needles, m.p. 220-222° (decomp.), a perchlorate of cubic crystals, m.p. 178-181° (decomp.), and a hydriodide of m.p. 217-219° (decomp.). The structure of this ether is similar to that of Benadryl but no antihistamine activity was found to be shown by it.