Molecular basis for the enhanced lipase-catalyzed N-acylation of 1-phenylethanamine with methoxyacetate
2006 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 7, no 11, 1745-1749 p.Article in journal (Refereed) Published
One of the commercial methods for preparing enantiopure amines is lipase-catalyzed kinetic resolution, although lipases catalyze, aminolysis with only low activity. Interestingly, in 1997 Balkenhohl et al. used, ethyl methoxyacetate instead of ethyl butyrate as an acylation reagent for the aminolysis of 1-phenylethanamine and increased the reaction rate more than a 100-fold. This method has been applied to other aminolysis reactions, but the molecular basis for the enhanced rate is not understood. A moecular-modeling study of the transition-state analogue for the aminolysis showed that an interaction between the beta-oxygen atom in methoxyacetate and the amine nitrogen atom might be a key factor in the rate enhancement. Other acylation reagents, such as methyl 3-methoxypropionate and methyl 4-methoxybutyrate, were chosen to test the influence of this interaction because these molecules can be spatially arranged to have similar to that in the acylation with methyoxyacetate. The initial aminolysis rates were improved (11-fold and sixfold, respectively) compared to that with butyrate. In with 1-phenylethanol afforded the same rate with all acyl donors.
Place, publisher, year, edition, pages
2006. Vol. 7, no 11, 1745-1749 p.
acylation, hydrogen bonds, kinetics, molecular modeling, phenylethanamine, kinetic resolution, nucleic-acids, binding-sites, force-field, triad forms, amines, subtilisin, proteins, esters
IdentifiersURN: urn:nbn:se:kth:diva-16130DOI: 10.1002/cbic.200600245ISI: 000242054600019ScopusID: 2-s2.0-33750994330OAI: oai:DiVA.org:kth-16130DiVA: diva2:334172
QC 201005252010-08-052010-08-05Bibliographically approved