The Trp 116 mutants of Old Yellow Enzyme 1 that catalyzed the redn. of (Z)-beta-aryl-beta-cyanoacrylates (Z)- RC(CN):CHCO2Me (R = Ph, 4-OMeC6H4, 4-ClC6H4, 4-BrC6H4, 4-FC6H4, 3-FC6H4, 2-FC6H4) (I) gave the opposite enantioselectivity according to the nature of the amino acid in position 116. Small amino acids (e.g., alanine) make the substrate bind to the enzyme's active site in a 'classical' orientation, afforded the (S)-enantiomer (S)- RCH(CN)CH2CO2Me (R = Ph, 4-OMeC6H4, 4-ClC6H4, 4-BrC6H4, 4-FC6H4, 3-FC6H4, 2-FC6H4) of the reduced product. When the size of the amino acid increases (e.g., leucine), a 'flipped' binding mode is adopted by the substrate, which is converted into the corresponding (R)-product (R)-RCH(CN)CH2CO2Me (R = Ph, 4-OMeC6H4, 4-ClC6H4, 4-BrC6H4, 4- FC6H4, 3-FC6H4, 2-FC6H4). The redn. does not occur with bulky amino acids (e.g., tryptophan in the wild-type). The enantiomerically enriched cyanopropanoates I (R = Ph, 4-ClC6H4) thus prepd. can be converted into the corresponding (S)- and (R)-beta-aryl-gamma-lactams such as (R)-4-aryl-2-pyrrolidinones (aryl = Ph, 4-ClC6H4), precursors of inhibitory neurotransmitters belonging to the class of amma-aminobutyric acids, by a simple functional group interconversion in a sequential one-pot procedure.

Opposite Enantioselectivity in the Bioreduction of (Z)-beta-Aryl-eta-cyanoacrylates Mediated by the Tryptophan 116 Mutants of Old Yellow Enzyme 1: Synthetic Approach to (R)- and (S)-beta-Aryl-gamma-lactams

BRENNA, MARIA ELISABETTA;CROTTI, MICHELE;GATTI, FRANCESCO GILBERTO;PARMEGGIANI, FABIO;SANTANGELO, SARA;
2015

Abstract

The Trp 116 mutants of Old Yellow Enzyme 1 that catalyzed the redn. of (Z)-beta-aryl-beta-cyanoacrylates (Z)- RC(CN):CHCO2Me (R = Ph, 4-OMeC6H4, 4-ClC6H4, 4-BrC6H4, 4-FC6H4, 3-FC6H4, 2-FC6H4) (I) gave the opposite enantioselectivity according to the nature of the amino acid in position 116. Small amino acids (e.g., alanine) make the substrate bind to the enzyme's active site in a 'classical' orientation, afforded the (S)-enantiomer (S)- RCH(CN)CH2CO2Me (R = Ph, 4-OMeC6H4, 4-ClC6H4, 4-BrC6H4, 4-FC6H4, 3-FC6H4, 2-FC6H4) of the reduced product. When the size of the amino acid increases (e.g., leucine), a 'flipped' binding mode is adopted by the substrate, which is converted into the corresponding (R)-product (R)-RCH(CN)CH2CO2Me (R = Ph, 4-OMeC6H4, 4-ClC6H4, 4-BrC6H4, 4- FC6H4, 3-FC6H4, 2-FC6H4). The redn. does not occur with bulky amino acids (e.g., tryptophan in the wild-type). The enantiomerically enriched cyanopropanoates I (R = Ph, 4-ClC6H4) thus prepd. can be converted into the corresponding (S)- and (R)-beta-aryl-gamma-lactams such as (R)-4-aryl-2-pyrrolidinones (aryl = Ph, 4-ClC6H4), precursors of inhibitory neurotransmitters belonging to the class of amma-aminobutyric acids, by a simple functional group interconversion in a sequential one-pot procedure.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11311/969813
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