Synthesis of new acylpseudopeptides analogous to n-acetylmuramyl dipeptide (MDP)

Abstract

The synthesis of new non-glycosylated derivatives of MOP is described. Acylpseudopenta- or hexapeptides, of general formula R 1,-XxxΨ[CH 2,O]-D(L)-Ala-Ala-D-Glu[Lys(R 2)-NHEt]-NH 2 were obtained in two configurational forms on the α-carbon of the pseudo-alanyl (or lactyl) residue. The A/-tenTiinal pan of these compounds (R 1-XxxΨ[CH 2O]- D(D-Ala) mimics some of the essential chemical functions of /V-acetylmuramic acid (Xxx = Gly or Ser) and is substituted either by a lauroyl, a f-butyloxycarbonyl or an acetyl moiety (R 1): R 2,is either an acetate counter-ion or a glycyl resi- due. The diastereoisomers were resolved by high performance liquid cromatography (HPLC) and their absolute configuration was determined by proton nuclear magnetic resonance (NMR) in dimethylsulfoxide (DMSO). This technique evidenced furthermore two hydrogen bonds present in the structure of MDP.