36 (±)-Clivonineおよび(±)-Clividineの合成研究

抄録

Clivonine and clividine, isolated from Clivia miniata Regel (Amaryllidaceae), are the alkaloids of group characterized by benzo-pyrano[3,4-g]indole structure. The synthesis of the alkaloids of the group has not been reported so far. Cycloaddition of fumaric acid and 3,4-methylenedioxyphenyl allyl carbinol in acetic anhydride for 4 hr. gave two stereo-isomeric anhydrides (13) and (14). Hydrolysis of them gave the corresponding acids. Re-cyclization of the acids with acetic an-hydride under reflux furnished stereospecifically the same trans-cis-anhydride (12). Confirmation of the stereo-structure of the anhydrides was provided from the synthesis of α-, β-, and δ-lycoranes. Treatment of (12) with methanol gave the half-esters (19) and (20). Treatment of the former with thionyl chloride followed by sodium azide gave the azide (22) which was converted to the urethane (32). The diazoketone (34) derived from the acid (33) was subjected to the Wolff rearrangement in methanol to afford the ester (35). Hydrolysis of (35) gave the acid (36) which was easily cyclised to the oxoindole (37). Treatment of (37) with chloromethyl methyl ether followed by silver acetate furnished the acetate (38). Reduction of the acetate with lithium amuminum hydride gave the amine (40). Osmium tetroxide oxidation of the amine resulted in the formation of the stereoisomeric triols (41) and (42). Oxidation of the former with manganese dioxide gave (±)-clividine (2). The latter gave (±)-clivonine (1) on oxidation with the same reagent.