880-21-7Relevant academic research and scientific papers
Benzotriazole-mediated synthesis of aza-peptides: En route to an aza-leuenkephalin analogue
Abo-Dya, Nader E.,Biswas, Suvendu,Basak, Akash,Avan, Ilker,Alamry, Khalid A.,Katritzky, Alan R.
, p. 3541 - 3552 (2013/05/23)
Novel N-(N-Pg-azadipeptidoyl)benzotriazoles 20a-e couple efficiently with α-amino acids 21a-e, dipeptides 22a-c, aminoxyacetic acid 23a, depsidipeptide 23b, and α-hydroxy-β-phenylpropionic acid 27 yielding, respectively, azatripeptides 24a-g, azatetrapeptides 25a,b, a hybrid azatripeptide with an oxyamide bond 26a, a hybrid azatetrapeptide with an ester bond 26b, and a hybrid azatripeptide with an ester bond 28. A new protocol for the synthesis of N-Pg-azatripeptides 33a,b and 35a,b, each containing a natural amino acid at the N-terminus, avoids the low coupling rates of the aza-amino acid residue and enables the solution-phase synthesis of an azaphenylalanine analogue of Leu-enkephalin 40.
NG-aminoguanidines from primary amines and the preparation of nitric oxide synthase inhibitors
Martin, Nathaniel I.,Beeson, William T.,Woodward, Joshua J.,Marletta, Michael A.
, p. 924 - 931 (2008/09/20)
A concise, general, and high-yielding method for the preparation of N G-aminoguanidines from primary amines is reported. Using available and readily prepared materials, primary amines are converted to protected N G-aminoguanidines in a one-pot procedure. The method has been successfully applied to a number of examples including the syntheses of four nitric oxide synthase (NOS) inhibitors. The inhibitors prepared were investigated as competitive inhibitors and as mechanistic inactivators of the inducible isoform of NOS (iNOS). In addition, one of the four inhibitors prepared, NG-amino-NG-2,2,2-trifluoroethyl-L-arginine 19, displays the unique ability to both inhibit NO formation and prevent NADPH consumption by iNOS without irreversible inactivation of the enzyme.
N- and C-terminal modifications of negamycin
Raju,Mortell, Kathleen,Anandan, Sampathkumar,O'Dowd, Hardwin,Gao, Hongwu,Gomez, Marcela,Hackbarth, Corinne,Wu, Charlotte,Wang, Wen,Yuan, Zhengyu,White, Richard,Trias, Joaquim,Patel, Dinesh V.
, p. 2413 - 2418 (2007/10/03)
Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program. An orthogonally protected β-amino acid derivative 3a was synthesized and used in parallel synthesis of negamycin derivatives on solid support. This advanced intermediate was also used for N- and C-terminal modifications using solution-phase methodologies. The N-terminal modifications have resulted in the identification of active analogues, whereas the C-terminal modifications resulted in complete loss of antibacterial activity. The N-methyl negamycin analogue, 19a, inhibits protein synthesis (IC50=2.3 μM), has antibacterial activity (Escherichia coli, MIC=16 μg/mL), and is efficacious in an E. coli murine septicemia model (ED50=16.3 mg/kg).
