Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus

Sodiq A. Nafiu; Masateru Takahashi; Etsuko Takahashi; Samir Hamdan; Musa M. Musa

doi:10.1002/ejoc.202000728

Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus

Sodiq A. Nafiu, Masateru Takahashi, Etsuko Takahashi, Samir Hamdan, Musa M. Musa

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Abstract

We developed a one-pot two-step deracemization approach for 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.

Original language	English (US)
Journal	European Journal of Organic Chemistry
DOIs	https://doi.org/10.1002/ejoc.202000728
State	Published - Jul 3 2020

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https://repository.kaust.edu.sa/bitstream/10754/664114/1/Decentralization_ejoc.202000728.pdf

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@article{c4950e77dc644cd7bcd37ae65d8a2ef7,

title = "Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus",

abstract = "We developed a one-pot two-step deracemization approach for 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.",

author = "Nafiu, {Sodiq A.} and Masateru Takahashi and Etsuko Takahashi and Samir Hamdan and Musa, {Musa M.}",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: The authors acknowledge the support provided by the Deanship of Scientific Research (DSR) at King Fahd University of Petroleum and Minerals (KFUPM) for funding this work through project number DF191007. The authors also thank Prof. Claire Vieille, from the Department of Microbiology and Molecular Genetics as well as Biochemistry and Molecular Biology at Michigan State University, for providing the plasmids of TeSADH.",

year = "2020",

month = jul,

day = "3",

doi = "10.1002/ejoc.202000728",

language = "English (US)",

journal = "European Journal of Organic Chemistry",

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publisher = "Wiley-VCH Verlag",

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TY - JOUR

T1 - Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus

AU - Nafiu, Sodiq A.

AU - Takahashi, Masateru

AU - Takahashi, Etsuko

AU - Hamdan, Samir

AU - Musa, Musa M.

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: The authors acknowledge the support provided by the Deanship of Scientific Research (DSR) at King Fahd University of Petroleum and Minerals (KFUPM) for funding this work through project number DF191007. The authors also thank Prof. Claire Vieille, from the Department of Microbiology and Molecular Genetics as well as Biochemistry and Molecular Biology at Michigan State University, for providing the plasmids of TeSADH.

PY - 2020/7/3

Y1 - 2020/7/3

N2 - We developed a one-pot two-step deracemization approach for 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.

AB - We developed a one-pot two-step deracemization approach for 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.

UR - http://hdl.handle.net/10754/664114

UR - http://doi.wiley.com/10.1002/ejoc.202000728

U2 - 10.1002/ejoc.202000728

DO - 10.1002/ejoc.202000728

M3 - Article

SN - 1434-193X

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

ER -

Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus

Abstract

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