In 2010, Kam and co-workers isolated two complex Strychnos-Strychnos type, bisindole alkaloids (—)-leucoridine A and C from the stem-bark of leuconotis griffithi. A concise biomimetic total syntheses of Strychnos-Strychnos type bis-indole alkaloids (—)-leucoridine A and C was accomplished from the biomimetic dimerization of (−)-dihydrovalparicine. En route to (−)-dihydrovalparicine, we also prepared known alkaloids (+)-geissoschizoline and (—)-dehydrogeissoschizoline from commercially available N-tosyl indole 3-carboxaldehyde. Key steps involve an in situ dimerization of (−)-dihydrovalparicine from (—)-1, 2-dehydrogeissoschizoline with trifluoroacetic acid in the presence of 4 Å molecular sieves. Hydrochloric acid mediated ring-opening of indolenine in (—)-leucoridine A to afford (—)-leucoridine C. To elucidate the mechanism of dimerization we employed DFT calculations, which favors a stepwise aza-Michael/spirocyclization sequence over the alternate hetero Diels-Alder cycloaddition reaction.

Biomimetic total syntheses of Bis-Strychnosindole alkaloids (—)-leucoridines A and C through the dimerization of (—)-dihydrovalparicine

252nd National Meeting (2016)

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