N-Acetyl-muramyl-peptides

This section deals exclusively with the synthesis of MDP (1) itself (20, 30, 33, 35, 44, 50). Details of earlier preparations of N-acetyl-muramyl-peptides (5, 8, 39), although dealing with analogues of MDP, are mentioned occasionally. 

In the synthesis of N-acetyl-muramyl-peptides, and obviously of MDP, the most frequently used protected muramyl derivative is 1-O-benzyl-4,6-O-benzylidene-N-acetyl-muramic acid. This allows the mild and possibly simultaneous elimination of the benzylidene group and the benzyl group. Starting from D-glucosamine, either a- or p-benzyl-4,6-0-benzylidene-N-acetyl-muramide can be obtained (Fig. 4) 17, 25, 53). In spite of its slower hydrogenolysis rate 44), the a-isomer which is easier to prepare is generally preferred (55, 44) to the p-isomer 50). 

Several different metltods were used to couple muramic acid with the peptide moiety. In the first synthesis of MDP, N-ethyl-5-phenyl-is-oxazolium-3 -sulfonate (Woodward s reagent K) was used (50). This condensing reagent had been applied in earlier preparations of various N-acetyl-muramyl-peptides (8, 39). A mixture of acetonitrile-dimethyl-formamide (2 1), is used as solvent but the protected muramic acid derivative is poorly soluble and the reaction does not always proceed well. 

MDP, as all the N-acetyl-muramyl-peptides, can be precipitated by addition of ether from its ethanol or methanol solution, but it occludes a considerable amount of solvent judging from elemental analysis. Repeated lyophilization allows the elimination of all traces of solvent 33). 

Das, B. C., and E. Nebelin Structural Characterization of N-acetyl-muramyl-peptides by mass spectrometry. In Peptides 1978 (I. Z. Siemon and G. Kupryszewski, Eds.). 

Kotani, S., Y. Watanabe, F. Kinoshita, T. Shimono, I. Marisaki, T. Shiba, S. Kusumoto, Y. Tarumi, and K. Ikenaka Immunoadjuvant activities of synthetic N-acetyl-muramyl-peptides or aminoacids. Biken J. 18, 105 (1975). 

LEFRANaER, P.. J. Choay. M. Derrien, and I. Lederman Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine, an adjuvant of the immune response and of some N-acetyl-muramyl-peptide analogs. Int. J. Peptide Protein Res. 9, 249 (1977). 

Tanaka, A., R. Saito, K. Sugiyama, I. Morisaki, S. Kotani, S. Kusumoto, and T. Shiba Adjuvant activity of synthetic N-acetyl-muramyl peptides in rats. Infect. Immun. 15, 332 (1977). 

Formation of the three-dimensional network of bacterial peptidoglycan includes synthesis both of glycosidic and peptide linkages, but only the former type of reaction is discussed in this Section. The assembly of the carbohydrate chains of a peptidoglycan has been shown to occur through a block mechanism. The initial reaction consists in transfer of N-acetyl-muramyl-pentapeptide phosphate from the corresponding UDP derivative... 

When UDP-2-acetamido-2-deoxy-D-glucose and UDP-N-acetyl-muramyl-pentapeptide are together added to broken bacterial-cell preparations, a new product is formed that contains the sugar and sugar-peptide portions of the precursors. If cells broken by means of a sonic oscillator are used, it is necessary to carry out the incubations on a filter-paper support " the precise function played by the filter paper is not yet known. In contrast, if enzymes are prepared by grinding cells with alumina, filter-paper support is unnecessary and the product contains a linear glycan backbone in which the two sugar residues occur in the alternate sequence expected. ... 

N-acetyl-B-D-glucosaminidase, alpha N-acetyl-B-D-glucosaminidase, beta N-acetyl-muramyl-L-alanine amidase Neuron-specific enolase Neutrophil-activating peptide 2 Osteocalcin Osteonectin... 

The synthesis of the N-acetyl-muramyl tetrapeptide (61) (33,44), which has the peptide sequence of the monomeric glycopeptide unit of many peptidoglycans, and that of its diastereoisomer (62) (45) has been reported. The fully protected tetrapeptide was prepared by coupling the two fragments BOC-L-Ala-D-isoGln and Lys(Z)-D-(or L)-Ala-OBzl by means of the mixed anhydride method. 

The muramyl-peptide analogues, N-t2-(D-glucos-3- -yl)propanoyl and -acetyl]-L-alanlne, (6) and (7) respectively, have been synthesized by standard procedure from l,2 5,6-di-0-lsopropylldene-o-... 

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