Premium
Computational Study of the Lipase‐Mediated Desymmetrisation of 2‐Substituted‐Propane‐1,3‐Diamines
Author(s) -
GarcíaUrdiales Eduardo,
Busto Eduardo,
RíosLombardía Nicolás,
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.200900412
Subject(s) - substituent , chemistry , nucleophile , aryl , lipase , intramolecular force , oxyanion hole , ring (chemistry) , methylene , enantioselective synthesis , stereochemistry , diamine , medicinal chemistry , organic chemistry , catalysis , enzyme , active site , alkyl
Abstract The enantioselectivity displayed by the lipase from Pseudomonas cepacia towards a wide range of prochiral 2‐substituted‐propane‐1,3‐diamines was studied by means of molecular dynamics simulations (MDS). In all cases the enzyme allows the recovery of the corresponding amino carbamates of R configuration. However, the enantioselectivity is only synthetically useful if no ortho substituent is present and the aromatic ring is directly bonded to the 2‐carbon of the 1,3‐diamine core. Analysis of the MDS trajectories revealed that the homologation of 2‐aryl substituents by means of a methylene group lowers enantioselectivity by alleviating the conformational tension of the slow‐reacting orientations due to unfavourable intramolecular contacts between the ortho carbons of the aryl group and the nucleophilic nitrogen, as well as between the chiral carbon and the oxyanion. Additionally, the relative solvent accessible surfaces of the atoms of the aryl ring nicely correlate with the effect of the location of the substituent on enantioselectivity.