title: Racemization during aminolysis of activated esters of N-alkoxycarbonylamino acids by amino acid anions in partially aqueous solvents and a tactic to minimize it.
abstract: Racemization during the aminolysis of activated esters of N-alkoxycarbonylamino acids by amino acid anions in aqueous dimethylformamide was examined by determining the epimeric products by high-performance liquid chromatography. Partial racemization occurred for a variety of esters, particularly when sodium hydrogen carbonate was used to generate the anion of D-valine. The racemization results from prolonged contact of unconsumed ester with the alkaline medium. Variation of the stoichiometry of reagents for reactions with N-benzyloxycarbonylphenylalanine (Z-Phe) 4-nitrophenyl ester revealed that racemization could be minimized by using Na2CO3 as base and a 50% excess of amino acid anion. An efficient synthesis of optically pure Z-L-Phe-D-Val-OH was achieved with a reaction time of 15 min.
authors.affiliation: Department of Biochemistry, University of Ottawa, Ontario, Canada.
authors.forename: N L
authors.initials: NL
authors.lastname: Benoiton
authors.forename: Y C
authors.initials: YC
authors.lastname: Lee
authors.forename: F M
authors.initials: FM
authors.lastname: Chen
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D004151:Dipeptides; C081922:N-benzyloxycarbonylphenylalanyl-valine; C081923:benzyloxycarbonylphenylalanine 4-nitrophenyl ester; D010649:Phenylalanine