Aminolysis of N-Acetylmuramic Acid Lactones by Amino Acid and Peptide Esters - A Synthetic Route to N-Acetylmuramoylamide Derivatives

Sa？etak Aminolysis of N-acetylmuramic acid (MurNAc) lactones, carrying different HO-6 substituents, with amino acid or peptide esters as nucleophiles was studied. The reaction of the protected (1-+ 6) linked GlcNAc-MurNAc lactone I with r.-alanine methyl ester, performed in dioxane in the presence of imidazole and tetra-n-hexylammonium benzoate (THAB), gives amoderate (42%) yield of the disaccharide-amide VI. This was converted into the 4-acetate VII, also prepared by coupling of the ~-(1-+6)-linked disaccharide acid V with Ala-OMe. Benzyl ？-glycosides of HO-6 acetylated, tritylated and benzylated MurNAc lactones (IX, XI, XVIII) were used in aminolysis reactions with Ala-OMe and Ala-Gly-OBzl under various conditions. It is shown that the presence of imidazole and THAB, as well as the nature of the solvent, have a significant influence on the formation of the respective muramoylamides X, XII, XIII and XIX, resp.; conditions were elaborated to obtain these compounds in satisfactory (60- -800/0) yields, Additional evidence that the lactone ring-opening proceeds without epimerisation at C-4 is provided