60668-66-8Relevant articles and documents
Preparation of N-acylated phosphonopeptides with free phosphonic group
Solodenko,Kasheva,Kukhar
, p. 1631 - 1641 (2007/10/02)
Aminoalkylphosphonic acids on heating with hexamethyldisilazane yield tris(trimethylsilyl) derivatives, which are used as amino components for the synthesis of N-acylated phosphonopeptides with free phosphonic group. These transformations proceed with complete retention of the stereoconfiguration of aminophosphonate moiety.
Synthesis and structure-activity relationships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid
Atherton,Hassall,Lambert
, p. 29 - 40 (2007/10/02)
Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis. A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1,Alafosfalin) is described. Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1. L stereochemistry is generally required for both components. Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanines, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P). Replacement of L-Ala in 1 by common and are amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P). Synthetic variation of these more potent dipeptides leads to decreased activity. Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1. Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide.