1027259-58-0Relevant academic research and scientific papers
A facile synthesis of N-protected 1-aminoalkylphosphonamidate derivatives
Xu,Fu
, p. 4137 - 4145 (2000)
N-protected 1-amino-alkylphosphonamidates were synthesized using one-pot reactions of benzyl carbamate, aldehydes and alkoxyphosphine dichlorides and then with amines in the presence of triethylamine.
A novel and convenient method for synthesizing unsymmetrical - Benzyloxycarbonyl-protected 1-amino-1-arylalkylphosphonate mixed diesters
Xu,Fu
, p. 1223 - 1226 (2001)
Unsymmetrical N-benzyloxycarbonyl-protected 1-amino-1-arylalkylphosphonate mixed diesters were synthesized using a one-pot reaction involving benzyl carbamate, aromatic aldehydes and alkoxydichlorophosphine, followed by treatment with alcohols in the presence of triethylamine. The reactions were followed by 31P NMR and a mechanism is proposed.
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.
