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A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine).

ABSTRACT: The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C-N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type.

SUBMITTER: Kou KGM

PROVIDER: S-EPMC6342194 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine).

Kou Kevin G M KGM Pflueger Jason J JJ Kiho Toshihiro T Morrill Louis C LC Fisher Ethan L EL Clagg Kyle K Lebold Terry P TP Kisunzu Jessica K JK Sarpong Richmond R

Journal of the American Chemical Society 20180619 26

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C-N bond formations using a reductive cyclization and a photochemical hydroamination to construct an ...[more]

PMID: 29889509

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