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. 2010 Aug 18;51(33):4400-4402.
doi: 10.1016/j.tetlet.2010.06.075.

Biocatalytic asymmetric formation of tetrahydro-β-carbolines

Peter Bernhardt  1 , Aimee R Usera, Sarah E O'Connor
Affiliations

Biocatalytic asymmetric formation of tetrahydro-β-carbolines

Peter Bernhardt et al. Tetrahedron Lett. .

Abstract

Strictosidine synthase triggers the formation of strictosidine from tryptamine and secologanin, thereby generating a carbon-carbon bond and a new stereogenic center. Strictosidine contains a tetrahydro-β-carboline moiety - an important N-heterocyclic framework found in a range of natural products and synthetic pharmaceuticals. Stereoselective methods to produce tetrahydro-β-carboline enantiomers are greatly valued. We report that strictosidine synthase from Ophiorrhiza pumila utilizes a range of simple achiral aldehydes and substituted tryptamines to form highly enantioenriched (ee >98%) tetrahydro-β-carbolines via a Pictet-Spengler reaction. This is the first example of aldehyde substrate promiscuity in the strictosidine synthase family of enzymes and represents a first step towards developing a general biocatalytic strategy to access chiral tetrahydro-β-carbolines.

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Figures

Figure 1
Figure 1
Pictet-Spengler reaction catalyzed by strictosidine synthase. The tetrahydro-β-carboline moiety is highlighted in red, the C-C bond formed is shown in bold, and the stereogenic center (C3) is marked with an asterisk.
Figure 2
Figure 2
A) Reaction sequence leading to 3. B) Computer generated models of two diastereomers of 14 docked in RsSTS (RsSTS numbering). Arrows highlight H-2 that is deprotonated to form 3.
See this image and copyright information in PMC

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