Premium
Hydrogen‐Bonding‐Driven Enantioselective Resolution against the Kazlauskas Rule To Afford γ‐Amino Alcohols by Candida rugosa Lipase
Author(s) -
Min Bora,
Park Jeemin,
Sim YongKyun,
Jung Suhyun,
Kim SeongHo,
Song Jae Kwang,
Kim Bum Tae,
Park Sang Youn,
Yun Jaesook,
Park Seongsoon,
Lee Hyuk
Publication year - 2015
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.201402563
Subject(s) - candida rugosa , enantioselective synthesis , chemistry , lipase , enantiomer , hydrogen bond , kinetic resolution , stereochemistry , enantiomeric excess , organic chemistry , catalysis , molecule , enzyme
Abstract Most lipases resolve secondary alcohols in accordance with the “Kazlauskas rule” to give the R enantiomers. In a similar manner to other lipases, Candida rugosa lipase (CRL) exhibits R enantioselectivity towards heptan‐2‐ol, although the enantiomeric ratio ( E ) is low ( E =1.6). However, unexpected enantioselectivity (i.e., S enantioselectivity, E =58) of CRL towards 4‐( tert ‐butoxycarbonylamino)butan‐2‐ol, which has a similar chain length to heptan‐2‐ol, has been observed. To develop a deeper understanding of the molecular basis for this unusual enantioselectivity, we have conducted a series of molecular modeling and substrate engineering experiments. The results of these computational and experimental analyses indicated that a hydrogen bond between the Ser450 residue and the nitrogen atom of the carbamate group is critical to stabilize the transition state of the S enantiomer.