289658-78-2Relevant academic research and scientific papers
A new synthesis of protected phosphonodipeptides with an N-terminal amino acid
Sikora, Dorota,Gajda, Tadeusz
, p. 3755 - 3761 (2007/10/03)
A new simple protocol for the direct synthesis of phosphonodipeptides from N-protected amino acids, diethyl 1-azidoalkylphosphonates and tertiary alkyl phosphine (Bu3P, Me3P) was developed. The method is general and the coupling occurred with good yield (42-97%). Depending on the phosphine used and/or mechanism operating during the condensation, the reaction can be accomplished at room temperature, or on heating in toluene. (C) 2000 Elsevier Science Ltd.
STUDIES ON THE SYNTHESIS OF CHEMOTHERAPEUTICS. PART XIII. SYNTHESIS AND BIOLOGICAL STUDIES ON PHOSPHONOPEPTIDES HAVING ALKYL-, PHENYL-, AND HETEROCYCLIC SUBSTITUENTS.
Kametani, Tetsuji,Suzuki, Yukio,Kigasawa, Kazuo,Hiiragi, Mineharu,Wakisaka, Kikuo,et al.
, p. 295 - 319 (2007/10/02)
New antibacterial phosphonopeptides (3) were synthesized in order to improve the stability against hydrolysis by peptidase and the antibacterial spectra.Synthesis of them was accomplished by condensation of the N-carbobenzoxyamino acid with diethyl aminoalkylphosphonate followed by deprotection and hydrolysis.The antibacterial activity was evaluated in a defined medium and the stability against hydrolysis by rat liver homogenates was examined.Chemical modification of the N-terminal amino acid moiety of the phosphonopeptide containing sulfur or oxygen atom at β- or γ-position of the N-terminal α-amino acid residue lost rapidly their in vivo activity in spite of the high in vitro activity.The para substituted phenylalanyl-1-aminoethyl-phosphonic acids showed higher stability and slightly lower activity compared with those of the corresponding ortho- and meta-substituted isomers.Some of these para-substituted compounds (e.g. 9β, 10β, and 19β) exhibited the same level of the biological activity as that of Alafosfalin (1) in potency of the activity, broadness of the spectrum, and the serum level in mice after peroral administration.Phosphonopeptides consisted of unnatural amino acids and aminomethylphosphonic acid showed generally the extended spectra and activities, but these compounds were very fragile to hydrolysis by peptidase.None of phosphonopeptides containing 2-aminoethylphosphonic acid had the activity.
STUDIES ON THE SYNTHESIS OF CHEMOTHERAPEUTICS. PART XI. SYNTHESIS AND ANTIBACTERIAL ACTIVITIES OF PHOSPHONOPEPTIDES
Kametani, Tetsuji,Kigasawa, Kazuo,Hiiragi, Mineharu,Wakisaka, Kikuo,Haga, Seiji,et al.
, p. 1205 - 1242 (2007/10/02)
A variety of phosphonopeptides, shown in 2 as a general formula, containg natural and/or unnatural amino acids were synthesized, and their in vitro antibacterial activities were examined.N-Protected amino acids were condensed with 1-amino-ethylphosphonic acid or its ester followed by deprotection and hydrolysis to give the requisite phosphonopeptides.Several compounds showed higher levels of activity against certain members of Gram-negative bacteria than those of Alafosfalin (1) as the standard phosphonopeptide.A brief discussion on structure-activity relationships is also described.
