144156-71-8Relevant academic research and scientific papers
β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine
Schlosser, Manfred,Brügger, Nadia,Schmidt, Werner,Amrhein, Nikolaus
, p. 7731 - 7742 (2007/10/03)
A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α- difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α- oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro- β-phenylalanine derivatives (4). Enantiomerically pure β,β- difluorophenylalanine (L-4a) was obtained when α,α-difluoro-α- phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pKa values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (Ki 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.
Conversion of α-keto esters into β,β-difluoro-α-keto esters and corresponding acids: A simple route to a novel class of serine protease inhibitors
Parisi,Gattuso,Notti,Raymo,Abeles
, p. 5174 - 5179 (2007/10/02)
The preparation of a series of β,β-difluoro-α-keto esters and corresponding acids RCF2COCO2R' (R=Me, Et, i-Pr, Bn, and Ph; R'=Et and H), designed as potential inhibitors of serine proteases, is described. The standard procedure developed consists in the initial formation of an α,α- difluoro ester from an α-keto ester, followed by a simple four-step sequence involving the synthesis of hemiacetal, cyanohydrin, and α-hydroxy ester difluorinated intermediates. This method provides an easy route to β,β- difluoro-α-keto esters and corresponding acids, via 'formal' insertion of a difluoromethylene group between the R substituent and the α-carbonyl group of a generic α-keto ester.
