Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones

Sarah E. Franz; Richard R. Watkins; Laura A. Wright; Blair A. Weaver; Ramon C. Hartage; Ion Ghiviriga; Giuseppe Gumina; Brent D. Feske

doi:10.1055/s-0033-1339282

Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones

Sarah E. Franz
, Richard R. Watkins
, Laura A. Wright
, Blair A. Weaver
, Ramon C. Hartage
, Ion Ghiviriga
, Giuseppe Gumina
, Brent D. Feske

Biochemistry, Chemistry & Physics

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

7 Scopus citations

Abstract

Asymmetric γ-hydroxy nitriles are valuable intermediates because hydrolysis of the nitriles can result in an intramolecular cyclization to chiral γ-lactones, which have a variety of biological uses. Starting with an assortment of different aldehydes (alkyl and aryl) a 4-step synthesis of γ-keto nitriles was developed. These prochiral substrates were then screened against a library of ketoreductases for their ability to stereoselectively reduce the carbonyl. Enzymes from the short chain dehydrogenase family showed activity and these enzymatic reactions were scaled up to produce a diverse set of chiral γ-lactones.

Original language	English
Article number	SS-2013-M0268-OP
Pages (from-to)	2171-2178
Number of pages	8
Journal	Synthesis
Volume	45
Issue number	15
DOIs	https://doi.org/10.1055/s-0033-1339282
State	Published - 2013

Scopus Subject Areas

Catalysis
Organic Chemistry

Keywords

asymmetric catalysis
asymmetric synthesis
enzymes
lactones
reduction

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10.1055/s-0033-1339282

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title = "Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones",

abstract = "Asymmetric γ-hydroxy nitriles are valuable intermediates because hydrolysis of the nitriles can result in an intramolecular cyclization to chiral γ-lactones, which have a variety of biological uses. Starting with an assortment of different aldehydes (alkyl and aryl) a 4-step synthesis of γ-keto nitriles was developed. These prochiral substrates were then screened against a library of ketoreductases for their ability to stereoselectively reduce the carbonyl. Enzymes from the short chain dehydrogenase family showed activity and these enzymatic reactions were scaled up to produce a diverse set of chiral γ-lactones.",

keywords = "asymmetric catalysis, asymmetric synthesis, enzymes, lactones, reduction",

author = "Franz, \{Sarah E.\} and Watkins, \{Richard R.\} and Wright, \{Laura A.\} and Weaver, \{Blair A.\} and Hartage, \{Ramon C.\} and Ion Ghiviriga and Giuseppe Gumina and Feske, \{Brent D.\}",

year = "2013",

doi = "10.1055/s-0033-1339282",

language = "English",

volume = "45",

pages = "2171--2178",

journal = "Synthesis",

issn = "0039-7881",

publisher = "Georg Thieme Verlag",

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TY - JOUR

T1 - Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones

AU - Franz, Sarah E.

AU - Watkins, Richard R.

AU - Wright, Laura A.

AU - Weaver, Blair A.

AU - Hartage, Ramon C.

AU - Ghiviriga, Ion

AU - Gumina, Giuseppe

AU - Feske, Brent D.

PY - 2013

Y1 - 2013

N2 - Asymmetric γ-hydroxy nitriles are valuable intermediates because hydrolysis of the nitriles can result in an intramolecular cyclization to chiral γ-lactones, which have a variety of biological uses. Starting with an assortment of different aldehydes (alkyl and aryl) a 4-step synthesis of γ-keto nitriles was developed. These prochiral substrates were then screened against a library of ketoreductases for their ability to stereoselectively reduce the carbonyl. Enzymes from the short chain dehydrogenase family showed activity and these enzymatic reactions were scaled up to produce a diverse set of chiral γ-lactones.

AB - Asymmetric γ-hydroxy nitriles are valuable intermediates because hydrolysis of the nitriles can result in an intramolecular cyclization to chiral γ-lactones, which have a variety of biological uses. Starting with an assortment of different aldehydes (alkyl and aryl) a 4-step synthesis of γ-keto nitriles was developed. These prochiral substrates were then screened against a library of ketoreductases for their ability to stereoselectively reduce the carbonyl. Enzymes from the short chain dehydrogenase family showed activity and these enzymatic reactions were scaled up to produce a diverse set of chiral γ-lactones.

KW - asymmetric catalysis

KW - asymmetric synthesis

KW - enzymes

KW - lactones

KW - reduction

UR - https://www.scopus.com/pages/publications/84880853590

U2 - 10.1055/s-0033-1339282

DO - 10.1055/s-0033-1339282

M3 - Article

SN - 0039-7881

VL - 45

SP - 2171

EP - 2178

JO - Synthesis

JF - Synthesis

IS - 15

M1 - SS-2013-M0268-OP

ER -

Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones

Abstract

Scopus Subject Areas

Keywords

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