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Synthesis 2019; 51(09): 1980-1988
DOI: 10.1055/s-0037-1610687
paper
© Georg Thieme Verlag Stuttgart · New York

The Ambidextrous Pictet–Spengler Reaction: Access to the (+)- or (–)-Enantiomers of the Bioactive C-19 Methyl-Substituted Sarpagine/Macroline/Ajmaline Alkaloids from Either d- or l-Tryptophan

M. Toufiqur Rahman
,
James M. Cook*
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N. Cramer Street, Milwaukee, WI 53211, USA   Email: capncook@uwm.edu
› Author AffiliationsWe gratefully acknowledge the NIH grants NS076517 and MH096463 for generous financial support.
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Publication History

Received: 10 November 2018

Accepted after revision: 18 December 2018

Publication Date:
18 February 2019 (online)

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Abstract

Depicted in the following is the proof of concept, which is important to illustrate the full potential of the ambidextrous Pictet–Spengler (P-S) reaction. Previously, both d-tryptophan and l-tryptophan were employed to synthesize the key intermediates toward the natural enantiomers of C-19 methyl-substituted alkaloids. Now the enantiomeric series of the same key intermediates could also be synthesized from both d- or l-tryptophan in high yield and optical purity via this P-S/Dieckmann protocol. One can make either the natural or the unnatural alkaloids from either of the chiral starting amino acid esters, stereo- and enantiospecifically for biological screening.

Key words

asymmetric Pictet–Spengler reaction - bioactive alkaloids - unnatural enantiomers - indole alkaloids - tetrahydro-β-carboline - bicyclo[3.3.1] framework

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610687.
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