The synthesis of fluorinated aminophosphonic acid inhibitors of alanine racemase

Studies on organophosphorus compounds 101. A facile synthetic route to trifluoromethylated aminophosphonic acids and phosphonopeptides

“…IR spectra were taken on a Shimadzu-440 spectrometer. 1 19 F NMR spectra were obtained on a Varian EM 360A spectrometer using CF 3 COOH as an external standard, positive for downfield shifts. EI-MS were obtained on a HP5989A mass spectrometer.…”

“…1 (3) was obtained also from 3b by reaction with CAN. In a 50 mL pear-shaped flask was charged 3b (0.8 g, 2.35 mmol) and acetonitrile (22 mL).…”

“…Introduction of a fluorine atom into a biologically active compound usually results, as a rule, in an enhancement of the activity of the parent molecule. Utilizing fluorinated acetic acid, Flynn et al [1] described the synthesis of b-fluorinated aminophosphonic acids, namely, bmonofluoro, b-difluoro-, and b-trifluoro-␣-aminoethylphosphonic acid and their action as inhibitors of alanine racemace. Gruss and Hagele [2], on the other hand, reported a general method leading to nuclear fluorinated N-phenyl-phenylglycine and demonstrated that (N-p-trifluoromethoxyphenyl)-phenylglycine showed remarkable insecticidal activity toward harmful and parasitic insects.…”

Catalytic Hydrogenation of α‐Iminophosphonates as a Method for the Synthesis of Racemic and Optically Active α‐Aminophosphonates

“…As a rule, the reduction is accomplished by sodium borohydrides NaBH-A C H T U N G T R E N N U N G (OAc) 3 [34] or NaBH 3 CN. [35][36][37] The reductive amination of a-ketophosphonic acids was carried out using NaBH 4 [38] or its tritium analogue NaB 3 H 4 . [39] An attempt to hydrogenate diethyl 1-(benzhydrylimino)-2,2-difluoroethylphosphonate by hydrogen in the presence of palladium on carbon was unsuccessful, [35] perhaps for steric reasons.…”

“…[35][36][37] The reductive amination of a-ketophosphonic acids was carried out using NaBH 4 [38] or its tritium analogue NaB 3 H 4 . [39] An attempt to hydrogenate diethyl 1-(benzhydrylimino)-2,2-difluoroethylphosphonate by hydrogen in the presence of palladium on carbon was unsuccessful, [35] perhaps for steric reasons. The catalytic hydrogenation of g-substituted a-iminopropenylphosphonates was published [30] while the present publication was in preparation.…”