60668-25-9Relevant articles and documents
Synthesis and antimicrobial evaluation of N D alanyl 1 aminoethylphosphonic acid
Huber III,Gilmore,Robertson
, p. 106 - 108 (1975)
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Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors
Cressina, Elena,Lloyd, Adrian J.,De Pascale, Gianfranco,James Mok,Caddick, Stephen,Roper, David I.,Dowson, Christopher G.,Bugg, Timothy D.H.
experimental part, p. 3443 - 3455 (2009/10/10)
Ligase MurM catalyses the addition of Ala from alanyl-tRNAAla, or Ser from seryl-tRNASer, to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNAAla showed no inhibition of MurM, but adenosine 3′-phosphonate analogues showed inhibition of MurM, the most active being a 2′-deoxyadenosine analogue (IC50 100 μM). Structure/function studies upon this analogue established that modification of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modification of the adenosine 5′-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria.
PREPARATION OF BENZYL N-BENZYLOXYCARBONYLAMINOPHOSPHONATES AND -AMINOPHOSPHONITES - THE SCOPE AND LIMITATIONS OF O-BENZYL-N,N'-DICYCLOHEXYLOISOUREA METHOD
Mucha, Artur,Kafarski, Pawel,Plenat, Francoise,Cristau, Henri-Jean
, p. 187 - 194 (2007/10/02)
Protection of the amino group of aminophosphonic and aminophosphonous acids with benzyl chloroformate followed by esterification of the N-protected derivatives with O-benzyl-N,N'-dicyclohexyloisoureas is described.The esterification of aminobenzylphosphonic and aminobenzylphosphonous acids was studied in some details in order to discuss the scope and limitation of this procedure.The differences in the reactions of aminoalkylphosphonic and aminoalkylphosphonous acids are pointed out.Key words: Aminobenzylphosphonic and -phosphonous acid, N-benzyloxycarbonyl derivatives, esterification, O-benzyl-N,N'-dicyclohexyloisourea, benzyl N-benzyloxycarbonylaminobenzylphosphonate and phosphonite.
