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Diversity-Oriented Approach Toward the Syntheses of Amaryllidaceae Alkaloids via a Common Chiral Synthon

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journal contribution
posted on 13.07.2018, 00:00 by Prachi Verma, Atish Chandra, Ganesh Pandey
Functionalized hydroindole (1), a common chiral synthon, for versatile transformations to synthesize a broad range of Amaryllidaceae alkaloids (AAs) including (−)-crinine, (−)-crinane, (−)-amabiline, (+)-mesembrine, (−)-maritidine, (−)-oxomaritidine, and (+)-mesembrane is reported. Scaffold 1 is found as a prime structural motif in a wide variety of the AAs and is a novel synthon toward designing a divergent route for the synthesis of these natural products. This is established in a few steps, starting from a chiral aza-bicyclo-heptene sulfone scaffold (2) via conjugate addition and concomitant stereoselective ring opening with allylmagnesium bromide, a key step that generates a crucial quaternary stereocenter, fixing the stereochemistry of the rest of the molecule at an early stage. One carbon truncation followed by intramolecular reductive amination led to the desired core 1 in a multigram scale.