雷公藤的合成.doc

Total syntheses of both racemic triptolide and the levo-stereoisomer have been reported. L-dehydroabietic acid is used as the starting material. The phenol derivative of this acid (I) is converted to the trifluoroacetate (II). The latter is transformed into the isocyanate (III) by means of Curtius degradation by treating with thionyl chloride and sodium azide successively, followed by heating in toluene. The tertiary amine (IV) is formed on treatment of the isocyanate with lithium aluminum hydride in in refluxing tetrahydrofuran, and then with formic acid - formaldehyde The amine is oxidized with m-chloro perhenzoic acid, and the corresponding N-oxide is formed. Cope elimination of the N-oxide gives the olefin compound (V). Treatment of the latter with osmium tetroxide and sodium periodate affords the ketone (VI). The enolate of the compound (VI), on being generated by lithium diisopropylamide is transformed into the beta-hydroxy compound (VII) with formaldehyde. After the alcohol function has been blocked, the product is treated successively with benzyloxymethyllithium and hydrochloric acid in tetrahydrofuran and the triol monobenzyl ether (VIII) is formed. The primary alcoholic group is oxidized to the aldehyde by chromic anhydride in pyridine, and the phenol is acetylated with acetic anhydride in pyridine, and compound (IX) is afforded. Dehydration of this compound gives the unsaturated aldehyde (X). On oxidation of the aldehyde to the carboxylic acid, and then hydrogenolysis of the benzyloxy group, lactonization (XI) occurs spontaneously. A carbonyl group (XII) is introduced by oxidation with chromic anhydride in acetic acid. The acetyl group of compound (XII) is removed by saponification and the carbonyl function is reduced with sodium borohydride, and the diol (XIII) results. Treatment of the diol with sodium periodate gives the epoxy dienone (XIV). The latter is transformed into the bisoxide (XV) on treatment with hydrogen peroxide. L-Triptonide (XVI) is aff