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Influence of the Nucleophile on the Candida antarctica Lipase B‐Catalysed Resolution of a Chiral Acyl Donor
Author(s) -
GarcíaUrdiales Eduardo,
RíosLombardía Nicolás,
MangasSánchez Juan,
GotorFernández Vicente,
Gotor Vicente
Publication year - 2009
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.200900204
Subject(s) - chemistry , nucleophile , candida antarctica , aminolysis , substituent , intramolecular force , amine gas treating , enantiomer , stereochemistry , lipase , hydrogen bond , medicinal chemistry , organic chemistry , catalysis , enzyme , molecule
The resolution of methyl (±)‐3‐hydroxypentanoate catalysed by Candida antarctica lipase B has been performed by using ammonia and benzyl amine as nucleophiles. In all cases, the lipase reacts faster with the R enantiomer of the ester, but when benzyl amine is used, the enantiomeric ratio is approximately three times as high as that measured for ammonia. The analysis of the molecular dynamics simulations carried out over the corresponding deacylation transition state analogues indicated specular binding modes between enantiomers that vary greatly upon the nucleophile used. For the case of ammonia, an intramolecular hydrogen bond between the β‐hydroxyl group and the protons of the nucleophile is established. However, the presence of the substituent in benzyl amine disrupts this interaction. Instead, the acyl chain binds to a more restrictive area of the protein where the higher number of contacts established with the side chains of Thr40, Gln157 and Ile189 have been identified as the reason for the higher enantioselectivity observed in the aminolysis reaction.