Asymmetric Synthesis of (-)-fosfomycin and its Trans- (1S,2S)-diastereomer Using a Biocatalytic Reduction as the Key Step

Christian P. Marocco; Erik V. Davis; Julie E. Finnell; Phung-Hoang Nguyen; Scott C. Mateer; Ion Ghiviriga; Clifford W. Padgett; Brent D. Feske

doi:10.1016/j.tetasy.2011.10.009

Asymmetric Synthesis of (-)-fosfomycin and its Trans- (1S,2S)-diastereomer Using a Biocatalytic Reduction as the Key Step

Christian P. Marocco, Erik V. Davis, Julie E. Finnell, Phung-Hoang Nguyen, Scott C. Mateer, Ion Ghiviriga, Clifford W. Padgett, Brent D. Feske

Biochemistry, Chemistry, & Physics

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Fosfomycin is a gram positive and gram negative antibiotic that contains an asymmetric epoxide. An enzyme library was screened for its ability to reduce dimethyl(1-chloro-2-oxopropyl)phosphonate to the corresponding asymmetric chlorohydrin. Homology models were built in MOE, which were shown to accurately model the enzyme-substrate complex displaying the stereoselectivity that we observed. Two enzymes, YDR368w and YHR104w, were chosen for the scale up and synthesis of fosfomycin and its trans-(1S,2S)-diastereomer.

Original language	American English
Journal	Tetrahedron Asymmetry
Volume	22
DOIs	https://doi.org/10.1016/j.tetasy.2011.10.009
State	Published - Jan 1 2011

Keywords

Asymmetric synthesis
Ensyme
Gram positive
Gram-negative bacteria
Homology modeling
Organic chemistry
Scaling up

DC Disciplines

Chemistry

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https://doi.org/10.1016/j.tetasy.2011.10.009

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title = "Asymmetric Synthesis of (-)-fosfomycin and its Trans- (1S,2S)-diastereomer Using a Biocatalytic Reduction as the Key Step",

abstract = "Fosfomycin is a gram positive and gram negative antibiotic that contains an asymmetric epoxide. An enzyme library was screened for its ability to reduce dimethyl(1-chloro-2-oxopropyl)phosphonate to the corresponding asymmetric chlorohydrin. Homology models were built in MOE, which were shown to accurately model the enzyme-substrate complex displaying the stereoselectivity that we observed. Two enzymes, YDR368w and YHR104w, were chosen for the scale up and synthesis of fosfomycin and its trans-(1S,2S)-diastereomer.",

keywords = "Asymmetric synthesis, Ensyme, Gram positive, Gram-negative bacteria, Homology modeling, Organic chemistry, Scaling up",

author = "Marocco, {Christian P.} and Davis, {Erik V.} and Finnell, {Julie E.} and Phung-Hoang Nguyen and Mateer, {Scott C.} and Ion Ghiviriga and Padgett, {Clifford W.} and Feske, {Brent D.}",

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doi = "10.1016/j.tetasy.2011.10.009",

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T1 - Asymmetric Synthesis of (-)-fosfomycin and its Trans- (1S,2S)-diastereomer Using a Biocatalytic Reduction as the Key Step

AU - Marocco, Christian P.

AU - Davis, Erik V.

AU - Finnell, Julie E.

AU - Nguyen, Phung-Hoang

AU - Mateer, Scott C.

AU - Ghiviriga, Ion

AU - Padgett, Clifford W.

AU - Feske, Brent D.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Fosfomycin is a gram positive and gram negative antibiotic that contains an asymmetric epoxide. An enzyme library was screened for its ability to reduce dimethyl(1-chloro-2-oxopropyl)phosphonate to the corresponding asymmetric chlorohydrin. Homology models were built in MOE, which were shown to accurately model the enzyme-substrate complex displaying the stereoselectivity that we observed. Two enzymes, YDR368w and YHR104w, were chosen for the scale up and synthesis of fosfomycin and its trans-(1S,2S)-diastereomer.

AB - Fosfomycin is a gram positive and gram negative antibiotic that contains an asymmetric epoxide. An enzyme library was screened for its ability to reduce dimethyl(1-chloro-2-oxopropyl)phosphonate to the corresponding asymmetric chlorohydrin. Homology models were built in MOE, which were shown to accurately model the enzyme-substrate complex displaying the stereoselectivity that we observed. Two enzymes, YDR368w and YHR104w, were chosen for the scale up and synthesis of fosfomycin and its trans-(1S,2S)-diastereomer.

KW - Asymmetric synthesis

KW - Ensyme

KW - Gram positive

KW - Gram-negative bacteria

KW - Homology modeling

KW - Organic chemistry

KW - Scaling up

UR - https://digitalcommons.georgiasouthern.edu/chem-facpubs/129

UR - https://doi.org/10.1016/j.tetasy.2011.10.009

U2 - 10.1016/j.tetasy.2011.10.009

DO - 10.1016/j.tetasy.2011.10.009

M3 - Article

SN - 0957-4166

VL - 22

JO - Tetrahedron Asymmetry

JF - Tetrahedron Asymmetry

ER -

Asymmetric Synthesis of (-)-fosfomycin and its Trans- (1S,2S)-diastereomer Using a Biocatalytic Reduction as the Key Step

Abstract

Keywords

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