Asymmetric synthesis of phenyl-ring-containing alcohols using Thermoanaerobacter ethanolicus W110A secondary alcohol dehydrogenase
Musa, Musa Mohammed
MetadataShow full item record
This dissertation includes five chapters. Chapter 1 includes introduction and literature review. Chapter 2 and chapter 3 are reprinted from published articles. Chapter 4 is submitted for publication. Chapter 5 includes conclusions. Chapter 2 of this dissertation describes an enantioselective asymmetric 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) in Tris-HCl buffer solution using 2-propanol (30%, v/v) as the cosolvent and cosubstrate. 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 in Tris-HCl buffer solution/acetone (90:10, v/v). Chapter 3 of this dissertation describes the aforementioned asymmetric reductions of hydrophobic ketones by using xerogel-immobilized W110A TeSADH in organic solvents, which were achieved 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. Chapter 4 of this dissertation describes the results when 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.