Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED

A scalable synthesis of (3S,4S)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usab...

Full description

Saved in:
Bibliographic Details
Published in:Organic process research & development 2024-12, Vol.28 (12), p.4467-4476
Main Authors: Bigot, Antony, Rabion, Alain, Landier, Jean-Bernard, Laronze, Geoffrey, Petit, Frédéric, Deprets, Stéphanie, Michot, Jean-Marc, Yuan, Changxia, Sun, Fenglai, Chen, Han, Hou, Longlei, Tang, Dalin
Format: Article
Language:English
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites cdi_FETCH-LOGICAL-a163t-6a9c1f8d6652258e382159c327dba829504fed7f25c796f88c5b88f0af7ee55a3
container_end_page 4476
container_issue 12
container_start_page 4467
container_title Organic process research & development
container_volume 28
creator Bigot, Antony
Rabion, Alain
Landier, Jean-Bernard
Laronze, Geoffrey
Petit, Frédéric
Deprets, Stéphanie
Michot, Jean-Marc
Yuan, Changxia
Sun, Fenglai
Chen, Han
Hou, Longlei
Tang, Dalin
description A scalable synthesis of (3S,4S)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3S,4S)-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.
doi_str_mv 10.1021/acs.oprd.4c00388
format article
fullrecord <record><control><sourceid>acs_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1021_acs_oprd_4c00388</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>i12780052</sourcerecordid><originalsourceid>FETCH-LOGICAL-a163t-6a9c1f8d6652258e382159c327dba829504fed7f25c796f88c5b88f0af7ee55a3</originalsourceid><addsrcrecordid>eNp1kM1OAjEUhSdGExHdu-wDMNh2aKfjDgF_IkaimLibXDqtFGcoaTsY3sTHtQRdurr35NxzcvMlySXBfYIpuQLp-3bjqv5AYpwJcZR0CKM4ZYK_H8cdiyzlhOPT5Mz7FcaYcUI7yfdoqRojoUawrtCNsfJPDzcbZyFKj4KNLpqsYR2MbZTb-_UOzVqnUNYbpGPj24UPJrRBVWiugoPlrnJWty7mxjGwhWC2CkFAgJ7aOphPU9sPBw16jV3qGs2XCs3sl3LIavT4MhmfJycaaq8ufmc3ebudzEf36fT57mE0nKZAeBZSDoUkWlScM0qZUJmghBUyo3m1AEELhgdaVbmmTOYF10JIthBCY9C5UoxB1k3woVc6671Tutw404DblQSXe7JlJFvuyZa_ZGOkd4jsnZVt3To--P_5DwK3f1Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED</title><source>American Chemical Society:Jisc Collections:American Chemical Society Read &amp; Publish Agreement 2022-2024 (Reading list)</source><creator>Bigot, Antony ; Rabion, Alain ; Landier, Jean-Bernard ; Laronze, Geoffrey ; Petit, Frédéric ; Deprets, Stéphanie ; Michot, Jean-Marc ; Yuan, Changxia ; Sun, Fenglai ; Chen, Han ; Hou, Longlei ; Tang, Dalin</creator><creatorcontrib>Bigot, Antony ; Rabion, Alain ; Landier, Jean-Bernard ; Laronze, Geoffrey ; Petit, Frédéric ; Deprets, Stéphanie ; Michot, Jean-Marc ; Yuan, Changxia ; Sun, Fenglai ; Chen, Han ; Hou, Longlei ; Tang, Dalin</creatorcontrib><description>A scalable synthesis of (3S,4S)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3S,4S)-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.</description><identifier>ISSN: 1083-6160</identifier><identifier>EISSN: 1520-586X</identifier><identifier>DOI: 10.1021/acs.oprd.4c00388</identifier><language>eng</language><publisher>American Chemical Society</publisher><ispartof>Organic process research &amp; development, 2024-12, Vol.28 (12), p.4467-4476</ispartof><rights>2024 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a163t-6a9c1f8d6652258e382159c327dba829504fed7f25c796f88c5b88f0af7ee55a3</cites><orcidid>0000-0003-3320-3755</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids></links><search><creatorcontrib>Bigot, Antony</creatorcontrib><creatorcontrib>Rabion, Alain</creatorcontrib><creatorcontrib>Landier, Jean-Bernard</creatorcontrib><creatorcontrib>Laronze, Geoffrey</creatorcontrib><creatorcontrib>Petit, Frédéric</creatorcontrib><creatorcontrib>Deprets, Stéphanie</creatorcontrib><creatorcontrib>Michot, Jean-Marc</creatorcontrib><creatorcontrib>Yuan, Changxia</creatorcontrib><creatorcontrib>Sun, Fenglai</creatorcontrib><creatorcontrib>Chen, Han</creatorcontrib><creatorcontrib>Hou, Longlei</creatorcontrib><creatorcontrib>Tang, Dalin</creatorcontrib><title>Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED</title><title>Organic process research &amp; development</title><addtitle>Org. Process Res. Dev</addtitle><description>A scalable synthesis of (3S,4S)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3S,4S)-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.</description><issn>1083-6160</issn><issn>1520-586X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kM1OAjEUhSdGExHdu-wDMNh2aKfjDgF_IkaimLibXDqtFGcoaTsY3sTHtQRdurr35NxzcvMlySXBfYIpuQLp-3bjqv5AYpwJcZR0CKM4ZYK_H8cdiyzlhOPT5Mz7FcaYcUI7yfdoqRojoUawrtCNsfJPDzcbZyFKj4KNLpqsYR2MbZTb-_UOzVqnUNYbpGPj24UPJrRBVWiugoPlrnJWty7mxjGwhWC2CkFAgJ7aOphPU9sPBw16jV3qGs2XCs3sl3LIavT4MhmfJycaaq8ufmc3ebudzEf36fT57mE0nKZAeBZSDoUkWlScM0qZUJmghBUyo3m1AEELhgdaVbmmTOYF10JIthBCY9C5UoxB1k3woVc6671Tutw404DblQSXe7JlJFvuyZa_ZGOkd4jsnZVt3To--P_5DwK3f1Q</recordid><startdate>20241220</startdate><enddate>20241220</enddate><creator>Bigot, Antony</creator><creator>Rabion, Alain</creator><creator>Landier, Jean-Bernard</creator><creator>Laronze, Geoffrey</creator><creator>Petit, Frédéric</creator><creator>Deprets, Stéphanie</creator><creator>Michot, Jean-Marc</creator><creator>Yuan, Changxia</creator><creator>Sun, Fenglai</creator><creator>Chen, Han</creator><creator>Hou, Longlei</creator><creator>Tang, Dalin</creator><general>American Chemical Society</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-3320-3755</orcidid></search><sort><creationdate>20241220</creationdate><title>Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED</title><author>Bigot, Antony ; Rabion, Alain ; Landier, Jean-Bernard ; Laronze, Geoffrey ; Petit, Frédéric ; Deprets, Stéphanie ; Michot, Jean-Marc ; Yuan, Changxia ; Sun, Fenglai ; Chen, Han ; Hou, Longlei ; Tang, Dalin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a163t-6a9c1f8d6652258e382159c327dba829504fed7f25c796f88c5b88f0af7ee55a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bigot, Antony</creatorcontrib><creatorcontrib>Rabion, Alain</creatorcontrib><creatorcontrib>Landier, Jean-Bernard</creatorcontrib><creatorcontrib>Laronze, Geoffrey</creatorcontrib><creatorcontrib>Petit, Frédéric</creatorcontrib><creatorcontrib>Deprets, Stéphanie</creatorcontrib><creatorcontrib>Michot, Jean-Marc</creatorcontrib><creatorcontrib>Yuan, Changxia</creatorcontrib><creatorcontrib>Sun, Fenglai</creatorcontrib><creatorcontrib>Chen, Han</creatorcontrib><creatorcontrib>Hou, Longlei</creatorcontrib><creatorcontrib>Tang, Dalin</creatorcontrib><collection>CrossRef</collection><jtitle>Organic process research &amp; development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bigot, Antony</au><au>Rabion, Alain</au><au>Landier, Jean-Bernard</au><au>Laronze, Geoffrey</au><au>Petit, Frédéric</au><au>Deprets, Stéphanie</au><au>Michot, Jean-Marc</au><au>Yuan, Changxia</au><au>Sun, Fenglai</au><au>Chen, Han</au><au>Hou, Longlei</au><au>Tang, Dalin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED</atitle><jtitle>Organic process research &amp; development</jtitle><addtitle>Org. Process Res. Dev</addtitle><date>2024-12-20</date><risdate>2024</risdate><volume>28</volume><issue>12</issue><spage>4467</spage><epage>4476</epage><pages>4467-4476</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>A scalable synthesis of (3S,4S)-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3S,4S)-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.</abstract><pub>American Chemical Society</pub><doi>10.1021/acs.oprd.4c00388</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-3320-3755</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 1083-6160
ispartof Organic process research & development, 2024-12, Vol.28 (12), p.4467-4476
issn 1083-6160
1520-586X
language eng
recordid cdi_crossref_primary_10_1021_acs_oprd_4c00388
source American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)
title Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T14%3A04%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chemical%20and%20Biochemical%20Approaches%20to%20an%20Enantiomerically%20Pure%203,4-Disubstituted%20Tetrahydrofuran%20Derivative%20at%20a%20Multikilogram%20Scale:%20The%20Power%20of%20KRED&rft.jtitle=Organic%20process%20research%20&%20development&rft.au=Bigot,%20Antony&rft.date=2024-12-20&rft.volume=28&rft.issue=12&rft.spage=4467&rft.epage=4476&rft.pages=4467-4476&rft.issn=1083-6160&rft.eissn=1520-586X&rft_id=info:doi/10.1021/acs.oprd.4c00388&rft_dat=%3Cacs_cross%3Ei12780052%3C/acs_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-a163t-6a9c1f8d6652258e382159c327dba829504fed7f25c796f88c5b88f0af7ee55a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true