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Unformatted text preview: TeSADH (Prelog ADH) ADPR I86A TeSADH (anti-Prelog ADH) R1 is more sterically hindered and has higher Cahn-Ingold-Prelog priority than R2 In this presentation, an enantioselective reduction of phenyl -ring-containing ketones to yield the corresponding optically active secondary alcohols by using W110A secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (W110A TeSADH) will be described. The resulting alcohols have S-configuration, in agreement with Prelog’s rule, in which the nicotinamide-adenine dinucleotide phosphate (NADPH) cofactor transfers its pro-R hydride to the Re face of the ketone. (R)-Alcohols, the anti-Prelog products, were obtained by enantiospecific oxidation of ( S)-alcohols through oxidative kinetic resolution of the rac-alcohols using W110A TeSADH. The asymmetric reduction of benzylic and heteroaryl ketones to the corresponding (R)-alcohols using I86A TeSADH is also described. This single amino acid mutation not only makes the active site of I86A TeSADH able to accommodate more sterically hindered substituents than those accommodated by wild -type TeSADH, but it also reverses the substrate stereospecificity of TeSADH. The aforementioned asymmetric reductions were also achieved by using xerogel-immobilized W110A TeSADH in organic solvents in comparable yields to those obtained using the free enzyme, and, in some cases, with higher enantioselectivities. The use of xerogel encapsulated ADH is a facile method as it allows the reuse of the enzyme, it makes it more stable, and it can affect its enantioselectivity by switching to organic solvents. In an effort to study the performance of ADHs in different reaction media, medium engineering, these transformations were performed in mono and biphasic systems containing either organic solvents or ionic liquids. Both yield and enantioselectivity for these transformations can be controlled by changing the reaction medium. The enzyme showed high tolerance to both water-miscible and -immiscible organic solvents and ionic liquids, which allows biotransformations to be conducted at high substrate concentrations. 188 3rd ICYC 2010 Universiti...
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This note was uploaded on 02/17/2011 for the course CHEMISTRY 101 taught by Professor Csr during the Spring '11 term at University of Louisville.
- Spring '11