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Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus
Author(s) -
Nafiu Sodiq A.,
Takahashi Masateru,
Takahashi Etsuko,
Hamdan Samir M.,
Musa Musa M.
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000728
Subject(s) - chemistry , enantiopure drug , stereospecificity , stereoselectivity , enantioselective synthesis , enantiomeric excess , alcohol dehydrogenase , enantiomer , mitsunobu reaction , alcohol , stereochemistry , chiral auxiliary , biocatalysis , alcohol oxidation , organic chemistry , combinatorial chemistry , catalysis , reaction mechanism
We developed a one‐pot sequential two‐step deracemization approach to chiral alcohols using two mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase ( Te SADH). This approach relies on consecutive non‐stereospecific oxidation of alcohols and stereoselective reduction of their prochiral ketones using two mutants of Te SADH with poor and good stereoselectivities, respectively. More specifically, W110G Te SADH enables a non‐stereospecific oxidation of alcohol racemates to their corresponding prochiral ketones, followed by W110V Te SADH‐catalyzed stereoselective reduction of the resultant ketone intermediates to enantiopure ( S )‐configured alcohols in up to > 99 % enantiomeric excess. A heat treatment after the oxidation step was required to avoid the interference of the marginally stereoselective W110G Te SADH in the reduction step; this heat treatment was eliminated by using sol‐gel encapsulated W110G Te SADH in the oxidation step. Moreover, this bi‐enzymatic approach was implemented in the stereoinversion of ( R )‐configured alcohols, and ( S )‐configured alcohols with up to > 99 % enantiomeric excess were obtained by this Mitsunobu‐like stereoinversion reaction.