Transformation of Indole Alkaloids. II. On the C/D Ring Opening and Closing Reactions of Indole Alkaloids and the Syntheses of Vobasine Type Alkaloids

Abstract

From the cyanogen bromide reaction of yohimbine (I) in ethanol-chloroform, 3R-ethoxy-3, 4-seco-cyanamide (II) had been obtained by Albright and Goldmann, ⁶ but it was found that the ratio of reaction products (R and S) depends on the molar ratio of ethanol to the substrate (Table I). Stereospecific ring closing reaction of IIIa and IIIb with hot acetic acid was found to yield I(=IVa) and pseudoyohimbine (IVb), respectively. A similar result was obtained for hirsutine (VI), which gave 3R- and 3S-ethoxy-3, 4-seco-cyanamide (VIIa and b). Both compounds underwent stereospecific ring closure to dihydrocorynantheine (VIIIa) and VI (=VIIIb), respectively. Treatment of gardnerine (XII) with BrCN resulted in the formation of its cyanamide ether (XIII). In the ring closing reaction with hot acetic acid, XIII gave a new iminoindolenine derivative (XIV). Two convenient routes are described for the syntheses of vobasine-type alkaloids from gardnerine acetate (XXVI). When phenyl chloroformate was used instead of BrCN, in a two-phase reaction with aqueous alkali and pure chloroform, N_a-methylgardnerine acetate (XXVII) directly provided an amorphous 3-hydroxy-3, 4-seco-urethane derivative (XXVIII) in 60-70% yield. XXVIII was converted to the desired 2-acylindole alkaloid (XXIX), mp 197 -199°, in two steps. Treatment of XXVI with BrCN in 10% methanolpure chloroform resulted in the formation of 3-methoxy-3, 4-seco-cyanamide (XXXIV). Oxidation of XXXIV with t-BuOCl gave 3-keto-3, 4-seco-cyanamide (XXXV) in 39% yield. XXXV was converted to the desired 2-acylindole alkaloid (XXXIX), mp 206.5-209°, in two steps.