3130-92-5Relevant academic research and scientific papers
Simultaneous enzymatic synthesis of (S)-3-fluoroalanine and (R)-3-fluorolactic acid
Goncalves,Antunes,Pinto,Oestreicher
, p. 1465 - 1468 (2000)
A coupled enzymatic system for the simultaneous synthesis of (S)-3-fluoroalanine (1a) and (R)-3-fluorolactic acid (3) with L-alanine dehydrogenase (L-AlaDH) from Bacillus subtilis and rabbit muscle L-lactate dehydrogenase (L-LDH) using rac-1 and NAD+ is described. Analysis of isolated products of the laboratory preparative scale process revealed 1a in 60% yield and 88% ee and 3 in 80% yield and over 99% ee. The compounds 1a and 3 represent chiral building blocks for the synthesis of several products with pharmacological activity. Copyright (C) 2000 Elsevier Science Ltd.
Thermodynamics and kinetic aspects involved in the enzymatic resolution of (R,S)-3-fluoroalanine in a coupled system of redox reactions catalyzed by dehydrogenases
Goncalves, Luciana P. B.,Antunes,Oestreicher, Enrique G.
, p. 673 - 677 (2012/12/22)
Two systems of redox enzymatic reactions were tested, looking forward to the preparation of (S)-3-fluoroalanine, a potent antibiotic, by kinetic resolution of rac-3-fluoroalanine. This starting material was the main substrate for the deaminative oxidation reaction catalyzed by L-alanine dehydrogenase (L-AlaDH) in the presence of NAD+. One system was formed by coupling this reaction (main reaction) to the reduction of 3-fluoropyruvate (a cascade system) produced in the main reaction catalyzed by L-lactate dehydrogenase (L-LDH) in the presence of NADH, also formed in the main reaction. This system, that was able to achieve 92% of conversion, allows the accumulation of NH 4+, one of the secondary products of the main reaction. The other coupled redox system involved the coupling to the L-AlaDH reaction to the aminative reduction reaction of α-ketoglutarate in the presence of NADH and NH4+ (both side products of the main reaction) catalyzed by L-glutamate dehydrogenase (L-GluDH), that allows accumulation of 3-fluoropyruvate. With this system, the extent of the reaction in the coupled system was only 22%. This big difference in the efficiency of both systems was identified as being the result of a different potency of the products that accumulates in both systems, acting as inhibitors of L-AlaDH. It was demonstrated that 3-fluoropyruvate is a much stronger inhibitor of L-AlaDH than NH4+. This fact, and not thermodynamic considerations, explains the results obtained with both systems.
Kinetic aspects involved in the simultaneous enzymatic synthesis of (S)-3-fluoroalanine and (R)-3-fluorolactic acid
Gon?alves, Luciana P.B.,Antunes, Octavio A.C.,Pinto, Gerson F.,Oestreicher, Enrique G.
, p. 219 - 227 (2007/10/03)
Desaminative oxidation of rac -3-fluoroalanine (rac-1) catalyzed by l-alanine dehydrogenase (l-ALADH) was studied by means of initial rate experiments both in the presence and in the absence of a product. Estimates of kinetic parameters of the reaction were obtained. The reaction mechanism is the sequential ordered BiTer mechanism with inhibition by excess of (S)-3-fluoroalanine. This kinetic study was the basis for the development of a couple enzymatic system for the simultaneous synthesis of (S)-3-fluoroalanine (1a) and (R)-3-fluorolactic acid (3) with l-ALADH and l-lactate dehydrogenase using rac-1 and NAD+. Analysis of isolated products revealed 1a in 60% yield and 86% ee and 3 in 80% yield and over 99% ee. Compounds 1a and 3 represent chiral building blocks for the synthesis of several products with pharmacological activity. The presence of the fluorine atom in the substrate causes a better interaction of it in the active site of the enzyme.
