150618-26-1Relevant academic research and scientific papers
Biomimetic Transamination of α-Alkyl β-Keto Carboxylic Esters. Chemoenzymatic Approach to the Stereochemically Defined α-Alkyl β-Fluoroalkyl β-Amino Acids
Soloshonok, Vadim A.,Soloshonok, Irina V.,Kukhar, Valery P.,Svedas, Vytas K.
, p. 1878 - 1884 (2007/10/03)
Biomimetic transamination of the commercially available ethyl 2-methyl-3-keto-4,4,4-trifluorobutyrate (4) with benzylamine was shown to provide a simple access to the 2-methyl-3-amino-4,4,4trifluorobutanoic acids, a hitherto unknown biologically relevant β-amino acid. In sharp contrast to the α-unsubstituted β-keto carboxylic esters the transamination of α-methyl β-keto carboxylic ester 4 proceeds under mild reaction conditions, presumably, due to relative instability of the intermediate (Z)-enamine 6. Diastereoselectivity of the process was found to be controlled by the nature of the base-catalyst allowing for a stereodivergent preparation of (2R*,3S*)-8a and (2R*,3R*)8b diastereomers as dominant reaction products. Preparation of all four diastereo- and enantiomerically pure optical isomers of the 2-methyl-3-amino-4,4,4-trifluorobutanoic acid was effectively accomplished by penicillin acylase-catalyzed resolution of the corresponding diastereomerically pure N-phenylacetyl derivatives. The whole process, a stereocontrolled chemoenzymatic approach, including the diastereoselective base-catalyzed [1,31-proton shift reaction and the enantioselective penicillin acylase-catalyzed resolution, employs a simple set of reactions, inexpensive reagents, and mild reaction conditions, that would render it methodologically useful for preparing biologically interesting α,β-disubstituted fluorinated β-amino acids.
Biomimetic base-catalyzed [1,3]-proton shift reaction. A practical synthesis of β-fluoroalkyl-β-amino acids
Soloshonok, Vadim A.,Kukhar, Valery P.
, p. 6953 - 6964 (2007/10/03)
An efficient approach to practical synthesis of β-fluoroalkyl-β-amino acids is described. The method consists in the reducing reagent-free base-catalyzed biomimetic transamination between fluorinated β-keto carboxylic esters and benzylamine. This transformation involves two sequential base-catalyzed [1,3]-proton transfers giving rise to corresponding N-benzylidene derivatives as the products of final thermodynamic equilibration, directed by the electron-withdrawing character of fluoroalkyl groups. Opportunity for catalytic enantiocontrolled synthesis of targeted β-amino acids with application of monochiral base, as a catalyst for these isomerizations, is demonstrated.
Transamination of Fluorinated β-Keto Carboxylic Esters. A Biomimetic Approach to β-Polyfluoroalkyl-β-amino Acids.
Soloshonok, Vadim A.,Kirilenko, Alexander G.,Kukhar', Valery P.,Resnati, Giuseppe
, p. 3621 - 3624 (2007/10/02)
The base-catalyzed isomerization of N-benzylimines (or enamines) of β-polyfluoroalkyl-β-ketocarboxylic esters cleanly affords the N-benzylidene derivatives of β-polyfluoro-β-aminocarboxylic esters which are hydrolyzed to corresponding amino acids in high overall yields.
