1. Monoamine Oxidase (MAO-N) Catalyzed Deracemization of Tetrahydro-β-carbolines: Substrate Dependent Switch in Enantioselectivity
- Author
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Anthony P. Green, Nicholas J. Turner, Simon C. Willies, Diego Ghislieri, and Deborah Houghton
- Subjects
biology ,010405 organic chemistry ,Reducing agent ,Chemistry ,Stereochemistry ,Monoamine oxidase ,Aspergillus niger ,Substituent ,Substrate (chemistry) ,Active site ,General Chemistry ,010402 general chemistry ,biology.organism_classification ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Biocatalysis ,biology.protein ,Enantiomeric excess - Abstract
The tetrahydro-β-carboline (THBC) ring system is an important structural motif found in a large number of bioactive alkaloid natural products. Herein we report a broadly applicable method for the synthesis of enantiomerically pure β-carbolines via a deracemization procedure employing the D9 and D11 variants of monoamine oxidase from Aspergillus niger (MAO-N) in combination with a nonselective chemical reducing agent. Biotransformations were performed on a preparative scale, leading to the synthesis of optically enriched products in excellent enantiomeric excess (e.e.; up to 99%) and isolated yield (up to 93%). Interestingly, a switch in enantioselectivity associated with the MAO-N variants is observed as the nature of the C-1 substituent of the THBC is varied. Molecular modeling provided an explanation for this observation and highlighted key active site residues which were modified, resulting in an increase in (R)-selectivity associated with the enzyme. These results provide insight into the factors whic...
- Published
- 2013