Przemyslaw Mastalerz

New phosphonic analogs of aspartic and glutamic acid by aminoalkylation of trivalent phosphorus chlorides with ethyl acetyloacetate or ethyl levulinate and benzyl carbamate

Preparation of the phosphonic analogs of α-methylaspartic (4 a–d), glutamic (7 a–b) and α-methylpyroglutamic (5 a–b) acids by aminoalkylation of trivalent phosphorus chlorides with ethyl esters of oxoalkyloacids and benzyl carbamate is described. The phosphonic analogs of pyroglutamic acid (8 a–b) was obtained by the cyclization of the corresponding esters (9 a–b). The stability of the phosphonic analogs of pyroglutamic acid in acidic and alkaline media was also studied.ZusammenfassungEs wurde die Darstellung der Phosphonanalogen der α-Methylasparaginsäure (4 a–d), Glutamin- (7 a–b) und α-Methylpyroglutaminsäure (5 a–b) in der Reaktion der trivalenten Phosphorchloride und der Oxoalkansäureethylester sowie des Benzylcarbaminats beschrieben. In der Ringschlußreaktion der Ester (9 a–b) erhält man Phosphonanaloge der Pyroglutaminsäure. Die Stabilität der Analogen der Pyroglutaminsäure wurde in sauren und alkalischen Medien geprüft.

Non-hydrolysable Phosphinic Analogues of Dipeptides

Abstract Peptide analogues 1 in which the phosphonamide group replaces the amide function are thought to mimic the tetrahedral intermediates and transition states in peptide hydrolysis. While pepti-des 1 are potent inhibitors of some peptidases, their unsefulness is limited by rapid hydrolysis of P-N bond in aqueous media. To circumvent the instability problem we designed peptide analogues 2 with a CH2 group inserted between the phosphorus and nitrogen atoms. Such structures are resistant to hydrolysis but it was interesting to see if they are similar enough to pepti-des to retain any affinity to enzyme active sites.

Antibacterial Activity of Peptides Related to Alafosfalin. The Effect of Varying the Aminophosphonate Fragment

Abstract A series of 32 dipeptides containing N-terminal alanine or leu-cine and a variety of racemic 1-aminoalkanephosphonic acids vere prepared by standard procedures and tested for growth inhibition of six bacterial species (Escherichia coli, Klebsiella aerogenes, Serratia mercescens, Staphylococcus aureus, Streptococcus faeca-lis and Bacillus subtilis). The aminophosphonate residues were racemic and included Va1P, LeuP, ProP, PheP, α-methyl-AlaP, Glu-α-P, O-methyl-DOPAP, cyclohexane-1-amino-1-phosphonic acid, t-LeuP, O-acetyl-SerP, and GlyP derivatives RCH(NH2)PO3H2 where R=cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adaman-tyl. N-Ala and N-Leu peptides of racemic AlaP were used as positive control. MIC and IC50 values indicate that the peptides containing 4-amino-4-phosphonobutyric acid (Glu-α-P) and α-methyl-AlaP are potent antibiotics, comparable in activity with LeuAlaP and AlaAlaP (Alafosfalin). Weak activity was observed for peptides of ProP, LeuP, ValP, PheP, cyclohexane-1-amino-1-phos...