130521-05-0Relevant articles and documents
The synthesis of DL-3,3-difluoroglutamic acid from a 3-oxoprolinol derivative
Hart,Coward
, p. 4917 - 4920 (1993)
DL-3,3-Difluoroglutamic acid was synthesized from a masked 3-hydroxyprolinol, 6-hydroxy-1-aza-3-oxabicyclo[3,3,0]octan-2-one, in eight steps. The described synthetic route expands the utility of fluoroproline derivatives as precursors of fluoroglutamic acids.
Synthesis and biological activity of folic acid and methotrexate analogues containing L-threo-(2S,4S)-4-fluoroglutamic acid and DL-3,3-difluoroglutamic acid
Hart, Barry P.,Haile, William H.,Licato, Nicholas J.,Bolanowska, Wanda E.,McGuire, John J.,Coward, James K.
, p. 56 - 65 (2007/10/03)
The stereospecific syntheses of L-threo-γ-fluoromethotrexate (1t) and L- threo-γ-fluorofolic acid (3t) are reported. Compounds 1t and 3t have no substrate activity with folylpoly-γ-glutamate synthetase isolated from CCRF- CEM human leukemia cells, and compound It inhibits human dihydrofolate reductase at similar levels as methotrexate. The synthesis of DL-3,3- difluoro-glutamic acid (6) and its incorporation into DL-β,β-difluorofolic acid (4) are also reported. Compound 4 acts as a better substrate for human CCRF-CEM folylpoly-γ-glutamate synthetase than folic acid (V/K = ca. 7-fold greater). Thus, replacement of the glutamate moiety of methotrexate and folic acid with 4-fluoroglutamic acid and 3,3-difluoroglutamic acid results in folates and antifolates with altered polyglutamylation activity.
δ,ε-Unsaturated β,β-Difluoro-α-keto Esters: Novel Synthesis and Utility as Precursors of β,β-Difluoro-α-amino Acids
Shi, Guo-qiang,Cai, Wei-ling
, p. 6289 - 6295 (2007/10/03)
Treatment of the hemiketals 6 formed from ethyl trifluoropyruvate and primary allylic alcohols with SOCl2 and pyridine readily afforded a number of α-chloro-β,β-trifluorolactyl allyl ethers 2.Subsequent reductive dechlorofluorination from 2 led to the formation of allyl-substituted difluoroenol pyruvyl ethers 3 whose Claisen rearrangement provided a convenient access to a variety of δ,ε-unsaturated β,β-difluoro-α-keto esters 4.As further transformation, direct conversion of β,β-difluoro-α-keto esters to the corresponding β,β-difluoro-α-amino acids was achieved by reductive amination of the corresponding α-keto acids with NH3*H2O/NaBH4.Furthermore, use of the prepared β,β-difluoro-α-keto ester 4a as a common precursor of other structurally related β,β-difluoro-α-amino acids was demonstrated by the synthesis of β,β-difluoroproline (18) and β,β-difluoroglutamic acid (23) through synthetic elaboration of its inherent double bond.
