b,b-Difluoro analogs of a-oxo-b-phenylpropionic acid and phenylalanine

A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes into a-aryl-a,a-difluoroacetaldehydes. Subsequent hydrocyanation, hydrolysis, oxidn. and again hydrolysis afforded b-aryl-b,b-difluoro-a-oxopropionic acids. Reductive amination transformed the oxo acids into a separable mixt. of a-hydroxy acids and racemic b,b-difluoro-b-phenylalanine derivs.. Enantiomerically pure b,b-difluorophenylalanine was obtained when a,a-difluoro-a-phenylacetaldehyde was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixt. thus produced hydrolyzed to the carboxamides which were found to be separable by fractional crystn. or chromatog. The pKa values of the b-aryl-b,b-difluoroalanines were measured and biol. profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid proved to be a potent (Ki 27 mM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis. [on SciFinder (R)]


Published in:
Tetrahedron, 60, 35, 7731-7742
Year:
2004
Keywords:
Note:
CAN 141:296269
34-2
Amino Acids, Peptides, and Proteins
Institut de Chimie moleculaire et biologique, Ecole federale polytechnique,Lausanne,Switz.
Journal
0040-4020
written in English.
762292-90-0P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and PKa of); 742692-47-3P Role: BSU (Biological study, unclassified), RCT (Reactant), SPN (Synthetic preparation), BIOL (Biological study), PREP (Preparation), RACT (Reactant or reagent) (prepn. and arogenate dehydratase inhibitory activity of); 76600-70-9 (Arogenate dehydratase) Role: BSU (Biological study, unclassified), BIOL (Biological study) (prepn. of difluoro analogs of oxophenylpropionic acid and phenylalanine); 100-42-5 (Styrene); 405-99-2 (4 Fluorostyrene); 1073-67-2 (4 Chlorostyrene); 2627-86-3; 2632-13-5 (2 Bromo 4' methoxyacetophenone); 7677-24-9 (Cyanotrimethylsilane) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of difluoro analogs of oxophenylpropionic acid and phenylalanine); 696-31-1P; 1786-36-3P; 106263-12-1P; 106732-61-0P; 108661-89-8P; 118887-66-4P; 129660-35-1P; 129973-51-9P; 133367-99-4P; 144156-69-4P; 144156-71-8P; 144156-72-9P; 144156-73-0P; 207799-86-8P; 207799-87-9P; 233280-91-6P; 242148-56-7P; 362610-07-9P; 362610-10-4P; 711017-40-2P; 743416-66-2P; 749204-27-1P; 762292-69-3P; 762292-70-6P; 762292-71-7P; 762292-72-8P; 762292-73-9P; 762292-74-0P; 762292-75-1P; 762292-76-2P; 762292-77-3P; 762292-78-4P; 762292-79-5P; 762292-80-8P; 762292-81-9P; 762292-82-0P; 762292-83-1P; 762292-84-2P; 762292-85-3P; 762292-88-6P; 762293-00-5P; 762293-04-9P; 762293-06-1P; 762293-07-2P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of difluoro analogs of oxophenylpropionic acid and phenylalanine); 73602-61-6 Role: RGT (Reagent), RACT (Reactant or reagent) (prepn. of difluoro analogs of oxophenylpropionic acid and phenylalanine); 501435-61-6P; 517920-76-2P; 541508-26-3P; 762292-95-5P; 762293-02-7P; 762293-09-4P; 762293-10-7P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of difluoro analogs of oxophenylpropionic acid and phenylalanine)
Other identifiers:
Laboratories:




 Record created 2006-03-03, last modified 2018-01-27


Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)