44 SYNTHETIC STUDIES ON INDOLE ALKALOIDS USING THE 1,6-DIHYDRO-3(2H)-PYRIDINONE AS A COMMON STARTING MATERIAL
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Formal syntheses of (±)-catharanthine, one of the Iboga alkaloids, and (±)-tabersonine, one of the Aspidosperma alkaloids, were achieved from N-ethoxycarbonyl-1,6-dihydro-3(2H)-pyridinone (1a) as a common starting material. The key intermediate (7) for the Iboga alkaloids was prepared by two routes. The first route involved haloform reaction of 12, obtained from 2. The second one consisted of the Claisen rearrangement of 17, the precursor of 1a, and the subsequent hydroboration-oxidation. Ketalization of 7c and the subsequent PCC oxidation gave 42, which was converted to 50 via 49. Cyclization of 50 with p-TsOH afforded the pentacyclic ketone (51), which had already been transformed into (±)-catharanthine. On the other hand, 1a was treated with ethylmagnesium bromide to give the 1,2-adduct (54) along with the 1,4-adduct (55). Allylic rearrangement of the former, followed by the Claisen rearrangement, afforded 57, which was acetalized, hydrolyzed, and condensed with β-indolylacetyl chloride to give 60. The aldehyde (60) was smoothly oxidized with Ag_2O to yield 61, which then cyclized with PPA to (±)-5,16-dioxo-14,15-dehydroquebrachamine (53), the key intermediate for (±)-tabersonine. Thus, 1,6-dihydro-3(2H)-pyridinone system has been proved to be a potential synthon to some indole alkaloids.
