title: Computational study of the lipase-mediated desymmetrisation of 2-substituted-propane-1,3-diamines.
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.
authors.affiliation: Departmento de Química Orgánica e Inorgánica, Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: García-Urdiales
authors.forename: Eduardo
authors.initials: E
authors.lastname: Busto
authors.forename: Nicolás
authors.initials: N
authors.lastname: Ríos-Lombardía
authors.forename: Vicente
authors.initials: V
authors.lastname: Gotor-Fernández
authors.forename: Vicente
authors.initials: V
authors.lastname: Gotor
mesh_terms: D001665:Binding Sites; D016956:Burkholderia cepacia / Q000201:enzymology; D002384:Catalysis; D020134:Catalytic Domain; D003959:Diamines / Q000737:chemistry* / Q000378:metabolism; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D003959:Diamines; D008049:Lipase