An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis

Paul S. Riehl; Jesmine Lim; James D. Finnigan; Simon J. Charnock; Todd K. Hyster

doi:10.1021/acs.oprd.2c00017

An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis

Paul S. Riehl, Jesmine Lim, James D. Finnigan, Simon J. Charnock, Todd K. Hyster

Research output: Contribution to journal › Review article › peer-review

10 Scopus citations

Abstract

Herein, we describe a chemoenzymatic synthesis of the bicyclic fragment of Darunavir. A ketoreductase was identified using metagenomic mining to catalyze a highly enantio- and diastereoselective dynamic kinetic resolution of a β-ketolactone. Subsequent lactone reduction with diisobutylaluminum hydride and phase transfer cyclization affords the bicyclic acetal fragment in 39% yield over four steps.

Original language	English (US)
Pages (from-to)	2096-2101
Number of pages	6
Journal	Organic Process Research and Development
Volume	26
Issue number	7
DOIs	https://doi.org/10.1021/acs.oprd.2c00017
State	Published - Jul 15 2022
Externally published	Yes

All Science Journal Classification (ASJC) codes

Physical and Theoretical Chemistry
Organic Chemistry

Keywords

antiviral
biocatalysis
dynamic kinetic resolution
ketoreductase

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10.1021/acs.oprd.2c00017

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title = "An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis",

abstract = "Herein, we describe a chemoenzymatic synthesis of the bicyclic fragment of Darunavir. A ketoreductase was identified using metagenomic mining to catalyze a highly enantio- and diastereoselective dynamic kinetic resolution of a β-ketolactone. Subsequent lactone reduction with diisobutylaluminum hydride and phase transfer cyclization affords the bicyclic acetal fragment in 39\% yield over four steps.",

keywords = "antiviral, biocatalysis, dynamic kinetic resolution, ketoreductase",

author = "Riehl, \{Paul S.\} and Jesmine Lim and Finnigan, \{James D.\} and Charnock, \{Simon J.\} and Hyster, \{Todd K.\}",

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doi = "10.1021/acs.oprd.2c00017",

language = "English (US)",

volume = "26",

pages = "2096--2101",

journal = "Organic Process Research and Development",

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T1 - An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis

AU - Riehl, Paul S.

AU - Lim, Jesmine

AU - Finnigan, James D.

AU - Charnock, Simon J.

AU - Hyster, Todd K.

PY - 2022/7/15

Y1 - 2022/7/15

N2 - Herein, we describe a chemoenzymatic synthesis of the bicyclic fragment of Darunavir. A ketoreductase was identified using metagenomic mining to catalyze a highly enantio- and diastereoselective dynamic kinetic resolution of a β-ketolactone. Subsequent lactone reduction with diisobutylaluminum hydride and phase transfer cyclization affords the bicyclic acetal fragment in 39% yield over four steps.

AB - Herein, we describe a chemoenzymatic synthesis of the bicyclic fragment of Darunavir. A ketoreductase was identified using metagenomic mining to catalyze a highly enantio- and diastereoselective dynamic kinetic resolution of a β-ketolactone. Subsequent lactone reduction with diisobutylaluminum hydride and phase transfer cyclization affords the bicyclic acetal fragment in 39% yield over four steps.

KW - antiviral

KW - biocatalysis

KW - dynamic kinetic resolution

KW - ketoreductase

UR - https://www.scopus.com/pages/publications/85125403126

UR - https://www.scopus.com/inward/citedby.url?scp=85125403126&partnerID=8YFLogxK

U2 - 10.1021/acs.oprd.2c00017

DO - 10.1021/acs.oprd.2c00017

M3 - Review article

AN - SCOPUS:85125403126

SN - 1083-6160

VL - 26

SP - 2096

EP - 2101

JO - Organic Process Research and Development

JF - Organic Process Research and Development

IS - 7

ER -

An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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