56892-87-6Relevant articles and documents
Phosphinic acid pseudopeptides analogous to glutamyl-γ-glutamate: Synthesis and coupling to pteroyl azides leads to potent inhibitors of folylpoly-γ-glutamate synthetase
Valiaeva,Bartley,Konno,Coward
, p. 5146 - 5154 (2007/10/03)
Several routes to a complex phosphinate phosphapeptide analogous to the γ-glutamyl peptide Gluγ-Glu have been investigated. Formation of γ-phosphono glutamate derivatives via addition of a phosphorus-based radical to protected vinylglycine was found to be of limited value because of the elevated temperatures required. Alkylation and conjugate addition reactions of trivalent phosphorus (PIII) species were investigated. In situ generation of bis-trimethylsilyl esters of phosphinous acids proved to be an effective route to phosphinates of modest structural complexity. However, this chemistry could not be extended to the incorporation of an amino acid moiety at the N-terminal side of the desired phosphinate. A successful synthesis of the target phosphinate phosphapeptide was effected using PIII chemistry and dehydrohalogenation to yield an α,β-unsaturated phosphinic acid ester, following which conjugate addition of diethylacetamido malonate and acid-mediated hydrolysis afforded the desired phosphinate phosphapeptide. Coupling of the unprotected phosphinate phosphapeptide with two acyl azides derived from folic acid and methotrexate led to the corresponding pteroylphosphapeptides of interest as possible mimics of tetrahedral intermediates in the reaction catalyzed by folylpolyglutamate synthetase.
Efficient syntheses of pyrofolic acid and pteroyl azide, reagents for the production of carboxyl-differentiated derivatives of folic acid
Luo, Jin,Smith, Michael D.,Lantrip, Douglas A.,Wang, Susan,Fuchs
, p. 10004 - 10013 (2007/10/03)
Reaction of folic acid (1) with excess trifluoroacetic anhydride provides access to both the previously unknown N10-(trifluoroacetyl)pyrrofolic acid (8) and pyrofolic acid (9). Reaction of either of these materials with hydrazine selectively affords pteroyl hydrazide (13), which may be oxidized to pteroyl azide (27) on a large scale (62% overall from I without the need for chromatography). Treatment of 27 with differentially protected glutamates provides a convenient and high-yielding synthesis of differentially protected, optically pure folates.
Methotrexate analogs. 6. Replacement of glutamic acid by various amino acid esters and amines
Chaykovsky,Brown,Modest
, p. 909 - 912 (2007/10/10)
A series of methotrexate (MTX) analogs was prepared in which the glutamic acid moiety is replaced by various amino acid esters and amines. The synthetic method consisted of the reaction of 4 amino 4 deoxy N10 methylpteroic acid with various reagents to form intermediate mixed anhydrides, which then reacted with amino acid esters or amines to give the MTX analogs. These compounds were tested for antibacterial activity against Streptococcus faecium and for antitumor activity against L1210 leukemia in mice. Several compounds showed significant antibacterial activity; the MTX homocysteinethiolactone and MTX aspartate analogs showed marginal in vivo antitumor activity.
