Selective construction of alkaloid scaffolds by alcohol-based direct and mild aerobic oxidative Pictet–Spengler reactions

Organic & Biomolecular Chemistry
2020.0

Abstract

Employing TBN/TEMPO as the catalysts and oxygen as the oxidant, the biologically and pharmaceutically significant tetrahydro-beta-carboline and beta-carboline alkaloid scaffolds that used to be obtained by multi-step processes can now be selectively obtained in only one-step via direct aerobic oxidative Pictet-Spengler reactions of tryptamines with alcohols under mild conditions, with water generated as the byproduct. In this reaction, TBN/TEMPO was interestingly found to be able to facilitate the cyclization step of the whole reaction. This method tolerates a variety of C- and N-substituted tryptamines, and both the more reactive benzylic and allylic alcohols and the less reactive aliphatic alcohols. This method can also be extended to dihydro-beta-carboline synthesis and applied to the more available and more economical tryptophan for beta-carboline synthesis, revealing its broad substrate scope and potential in synthetic applications.

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