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Regio‐ and Enantioselective Sequential Dehalogenation of rac ‐1,3‐Dibromobutane by Haloalkane Dehalogenase LinB
Author(s) -
Gross Johannes,
Prokop Zbyněk,
Janssen Dick,
Faber Kurt,
Hall Mélanie
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600227
Subject(s) - chemistry , halogenation , nucleophile , hydrolysis , enantioselective synthesis , diol , enantiomer , regioselectivity , stereochemistry , biocatalysis , medicinal chemistry , catalysis , organic chemistry , reaction mechanism
The hydrolytic dehalogenation of rac ‐1,3‐dibromobutane catalyzed by the haloalkane dehalogenase LinB from Sphingobium japonicum UT26 proceeds in a sequential fashion: initial formation of intermediate haloalcohols followed by a second hydrolytic step to produce the final diol. Detailed investigation of the course of the reaction revealed favored nucleophilic displacement of the sec ‐halogen in the first hydrolytic event with pronounced R enantioselectivity. The second hydrolysis step proceeded with a regioselectivity switch at the primary position, with preference for the S enantiomer. Because of complex competition between all eight possible reactions, intermediate haloalcohols formed with moderate to good ee (( S )‐4‐bromobutan‐2‐ol: up to 87 %). Similarly, ( S )‐butane‐1,3‐diol was formed at a maximum ee of 35 % before full hydrolysis furnished the racemic diol product.