A.I. Ayi

New synthetic routes to β-fluoro β-phenyllactic acid derivatives and β-fluorocyanohydrins

Abstract Alkyl phenyl 2,3-epoxycarboxylates from the well-known Darzens glycidic esters synthesis react under very mild conditions with pyridinium-poly-hydrogen fluoride to give corresponding 3-fluoro 3-phenyllactates in almost quantitative yields with a high regio and stereoselectivity. This method can be applied successfully to other glycidic derivatives : glycidoamides, glycidonitriles, glycidoiminoesters… The spectrometric propertities (IR, NMR) are presented.

Synthesis and anti-HIV activity of some novel arylphosphate and H-phosphonate derivatives of 3′-azido-2′,3′-dideoxythymidine and 2′,3′-didehydro-2′,3′-dideoxythymidine

Phosphate and H-phosphonate derivatives of anti-HIV nucleoside analogues (AZT and d4T) were prepared as potential prodrugs of the bio-active free nucleotide and they were evaluated for their inhibitory effects on the replication of HIV-1 in several cell culture systems. One compound exhibited an important anti-HIV-1 activity and proved to be significantly more efficient than the parent nucleoside.

Monofluoration quantitative par le phenyltetrafluorophosphorane influence de la température

Abstract The monofluorination by substitution of the hydroxyl group of the β-hydroxyesters of (o, m, p) Z - C 6 H 4 - C(OH)R - CH R′ - COOR″ structure (where Z = halogen, methyl, methoxy, nitro and H) of 2,2,2 trichloroarylcarbinols by the phenyl tetrafluorophosphorane is described. The temperature at which the alkoxytrifluorophosphorane is decomposed, determines the nature (alkene alkoxytrifluorophosphorane, monofluorinated compounds) of the products and their yield. Knowledge of this temperature for erythro and threo isomers permits the selective fluorination of one them in a mixture.

Enzymatic hydrolysis of methyl 3,3-difluoro-2-amino esters. Synthesis of d- and l-3,3-difluoro-2-amino acids and their derivatives

Abstract The hydrolysis of methyl d,l -3,3-difluorophenyl alanate (1a) and methyl d,l -3,3-difluoro-2-aminobutanoate (1b) and their N-acetyl derivatives 2a and 2b by subtilisin has been studied. All derivatives examined were enzymatically resolved to separable mixtures of the corresponding 3,3-difluoro- l -amino acids (3a and 3b) or N-acetylamino acids (5a and 5b) and the unchanged 3,3-difluoro d -amino esters (4a and 4b) or N-acetylamino esters (6a and 6b). Acidic hydrolysis of methyl 3,3-difluoro- d -phenyl alanate (4a) or its N-acetyl derivative 6a led to 3,3-difluoro- d -phenyl alanime (8a). In the same manner, l - and d -2-amino-3,3-difluorobutanoic acids 7b and 8b were prepared starting from 5b and 6b. Optical purity and enantiomeric excess were determined by GC analysis of the N-acetyl esters and by NMR analysis determined in the presence of Eu(tfc)3. By these methods, unchanged methyl 3,3-difluoro- d -amino ester derivatives showed an ee of ≥ 90% while l -amino acids were estimated to have ≥ 95% ee.

Monofluoration stereoselective par le phenyltetrafluorophosphorane (PhPF4) Part. II. Application a la synthese des isomeres thréo et érythro des alkyl-2 fluoro-3 phenylpropanoates de methyle. Analyse conformationnelle par R.M.N. de 19F et 1H.

Abstract The stereoselective fluorination of four couples of diastereoisomeric 2-alkyl 3-hydroxy 3-phenylpropanoic methyl esters by the reaction of the phenyltetrafluorophosphorane with the corresponding trimethylsilylethers derivatives is described. The structure of the 2-alkyl 3-fluoro 3-phenyl propanoic methyl esters obtained quantitativly has been determined unambiguously by NMR analysis. 19 F NMR results permit us to determine the relative populations of the rotamers for each of the isomers threo and erythro.

A novel synthesis of 3-fluorophenylalanine and some of its derivatives

Abstract Ring opening of 2-cyano-3-phenylaziridine and 2-amido-3-phenylaziridine by HF/pyridine was found to give 2-amino-3-fluorophenylpropionitrile (IV) and 2-amino-3-fluorophenylalanamide (VII) respectively. 3-fluorophenylalanine (V) could be obtained by an acidic hydrolysis of (IV) or (VII) whereas isopropyl-3 fluorophenylalanate (VI) was isolated by esterification of (V) or by heating (IV) with iso-propanal-12 NHCl under reflux.

Reaction of o-arylenediamines with ethyl 3-fluoro 2-ketoesters synthesis of quinoxaline derivatives

Abstract The reaction of o-arylenediamines with ethyl 3-fluoro-2-ketoesters was studied. Fluoroquinoxaline derivatives characterized by their spectroscopic properties, were obtained in good yields. I.R. spectra, in particular, presented a very strong band at 1660–1667 cm −1 characteristic of ν C=O amide, indicating that the condensation products exist predominately in the keto form.

The synthesis of derivatives of 3-fluoro-2-ketoacids

Abstract 3-Fluoro-2-hydroxynitriles I a–h were found to be versatile intermediates to the 3-fluoropyruvic acids II a–h via a new method for the synthesis of these important compounds. Treatment of II a–h with diazomethane in anhydrous ether Ied to the corresponding methyl pyruvates. According to previously described routes we have obtained one 3-fluoro-2-aminoacid.

Fluorinated amino acids and peptides. Synthesis of 3,3-difluoro-2-amino acids, peptides and cyclodipeptides incorporating 3,3-difluoro-2-aminobutyric acid or 3,3-difluorophenylalanine residues in their structures

Abstract Convenient syntheses have been developed for N -9-fluorenylmethyloxycarbonyl-DL-2-amino-3,3-difluoro-butanoic acid and N -9-fluorenylmethyloxycarbonyl-DL-3,3-difluorophenylalanine which have been successfully introduced into peptide syntheses. Several fluorinated peptides have been obtained either by active ester coupling methods, mixed anhydride synthesis or with the aid of dicyclohexylcarbodiimide (DCC) in presence of 1-hydroxybenzotriazole (HOBt). The method has been applied to the preparation of seven hitherto unpublished representative 3-(1,1′-difluoroalkyl)-2,5-dioxopiperazines for biological purposes and structural chemistry studies.

New synthetic routes to β-fluoro-α-aminoacids B - from glycidonitriles

Abstract Ring opening of the glycidonitriles (II a–e) by HF/pyridine leads to the fluorocyanohydrins (III a–e). Treatment of the fluorocyanohydrins with ammonia in anhydrous methanol gives the α-amino-β-fluoronitriles (IV a–e) which upon acidic hydrol sis afford the β-fluoro-α-aminoacids (V a–e) in good overall yield.