Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate
Abstract Both enantiomers of optically pure 4‐bromo‐3‐hydroxybutanoate, which is an important chiral building block in the syntheses of various biologically active compounds including statins, were synthesized from rac ‐4‐bromomethyl‐β‐lactone through kinetic resolution. Candida antarctica lipase B...
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crwiley:10.1002/adsc.201200901 2024-09-15T17:46:25+00:00 Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate Lim, Jung Yun Jeon, Nan Young Park, A‐Reum Min, Bora Kim, Bum Tae Park, Seongsoon Lee, Hyuk 2013 http://dx.doi.org/10.1002/adsc.201200901 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fadsc.201200901 https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.201200901 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Advanced Synthesis & Catalysis volume 355, issue 9, page 1808-1816 ISSN 1615-4150 1615-4169 journal-article 2013 crwiley https://doi.org/10.1002/adsc.201200901 2024-08-09T04:22:06Z Abstract Both enantiomers of optically pure 4‐bromo‐3‐hydroxybutanoate, which is an important chiral building block in the syntheses of various biologically active compounds including statins, were synthesized from rac ‐4‐bromomethyl‐β‐lactone through kinetic resolution. Candida antarctica lipase B (CAL‐B) enantioselectively catalyzes the ring opening of the β‐lactone with ethanol to yield ethyl ( R )‐4‐bromo‐3‐hydroxybutanoate with high enantioselectivity ( E >200). The unreacted ( S )‐4‐bromomethyl‐β‐lactone was converted to ethyl ( S )‐4‐bromo‐3‐hydroxybutanoate (>99% ee ), which can be further transformed to ethyl ( R )‐4‐cyano‐3‐hydroxybutanoate, through an acid‐catalyzed ring opening in ethanol. Molecular modeling revealed that the stereocenter of the fast‐reacting enantiomer, ( R )‐bromomethyl‐β‐lactone, is ∼2 Å from the reacting carbonyl carbon. In addition, the slow‐reacting enantiomer, ( S )‐4‐bromomethyl‐β‐lactone, encounters steric hindrance between the bromo substituent and the side chain of the Leu278 residue, while the fast‐reacting enantiomer does not have any steric clash. Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library Advanced Synthesis & Catalysis 355 9 1808 1816 |
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Wiley Online Library |
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English |
description |
Abstract Both enantiomers of optically pure 4‐bromo‐3‐hydroxybutanoate, which is an important chiral building block in the syntheses of various biologically active compounds including statins, were synthesized from rac ‐4‐bromomethyl‐β‐lactone through kinetic resolution. Candida antarctica lipase B (CAL‐B) enantioselectively catalyzes the ring opening of the β‐lactone with ethanol to yield ethyl ( R )‐4‐bromo‐3‐hydroxybutanoate with high enantioselectivity ( E >200). The unreacted ( S )‐4‐bromomethyl‐β‐lactone was converted to ethyl ( S )‐4‐bromo‐3‐hydroxybutanoate (>99% ee ), which can be further transformed to ethyl ( R )‐4‐cyano‐3‐hydroxybutanoate, through an acid‐catalyzed ring opening in ethanol. Molecular modeling revealed that the stereocenter of the fast‐reacting enantiomer, ( R )‐bromomethyl‐β‐lactone, is ∼2 Å from the reacting carbonyl carbon. In addition, the slow‐reacting enantiomer, ( S )‐4‐bromomethyl‐β‐lactone, encounters steric hindrance between the bromo substituent and the side chain of the Leu278 residue, while the fast‐reacting enantiomer does not have any steric clash. |
format |
Article in Journal/Newspaper |
author |
Lim, Jung Yun Jeon, Nan Young Park, A‐Reum Min, Bora Kim, Bum Tae Park, Seongsoon Lee, Hyuk |
spellingShingle |
Lim, Jung Yun Jeon, Nan Young Park, A‐Reum Min, Bora Kim, Bum Tae Park, Seongsoon Lee, Hyuk Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate |
author_facet |
Lim, Jung Yun Jeon, Nan Young Park, A‐Reum Min, Bora Kim, Bum Tae Park, Seongsoon Lee, Hyuk |
author_sort |
Lim, Jung Yun |
title |
Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate |
title_short |
Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate |
title_full |
Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate |
title_fullStr |
Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate |
title_full_unstemmed |
Experimental and Computation Studies on Candida antarctica Lipase B‐Catalyzed Enantioselective Alcoholysis of 4‐Bromomethyl‐β‐lactone Leading to Enantiopure 4‐Bromo‐3‐hydroxybutanoate |
title_sort |
experimental and computation studies on candida antarctica lipase b‐catalyzed enantioselective alcoholysis of 4‐bromomethyl‐β‐lactone leading to enantiopure 4‐bromo‐3‐hydroxybutanoate |
publisher |
Wiley |
publishDate |
2013 |
url |
http://dx.doi.org/10.1002/adsc.201200901 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fadsc.201200901 https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.201200901 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Advanced Synthesis & Catalysis volume 355, issue 9, page 1808-1816 ISSN 1615-4150 1615-4169 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/adsc.201200901 |
container_title |
Advanced Synthesis & Catalysis |
container_volume |
355 |
container_issue |
9 |
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1808 |
op_container_end_page |
1816 |
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1810494546172182528 |