Abstract
As parts of the continuous studies on various alkaloids syntheses using a common synthon, ethyl 1,6-dihydro-3(2H)-pyridinone-1-carboxylate (1), we have achieved total synthesis of (±)-ibogamine (6), (±)-epiibogamine (7), and (±)-tecomanine (9) as follows. 1. Total Synthesis of 6 and 7 The alcohol (11) which had been obtained from 1 was transformed to the benzyl urethane (12). Hydrolysis of 12 followed by condensation with the ylid of triethyl phosphonoacetate yielded 14, which was oxidized to the keto ester (10). The base-catalyzed intra-molecular Michael addition of 10 gave 18a and 18b. The isomer (18a) was also obtained as the main product in the following sequence: 21→22→23→18a,b. Both the isomers were converted to the pentacyclic intermediates (32a,b) by several steps. An efficient one-step synthesis of (±)-ibogamine (6) and (±)-epiibogamine (7) from 32a and 32b, respectively, was able to be accomplished with a lithium aluminum hydride-aluminum chloride. 2. Total Synthesis of 9 Reaction of 1 with MeMgI gave 34 with a small amount of 33. Treatment of the former with ethyl propenyl ether in the presence of Hg(OAc)_2 at 200°afforded the aldehyde (52), which was derived to the diketone (58a,b) by the several steps via 56a,b. A careful treatment of 58a,b with K_2CO_3 in ethanol at 45-50°gave the desired product (60) as a sole isomer in 87-88% yield. Reduction of 60 with LiAlH_4 and subsequent oxidation with PCC gave (±)-tecomanine (9). Thus, the first and stereoselective total synthesis of 9 has been achieved.
