Protected N-acetyl-muramyl Derivatives

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). 

The preparation of 4,6-O-anisylidene-N-acetyl-muramic acid, without protection at C-1, but bearing an easily removable blocking group at C-4 and C-6, was reported (55). Recently, l-a-benzyl-4,6-0-isopropyli-dene-N-acetyl-muramide has been prepared 20). 

Couplii of Protected Muramic Acid and IMpeptide Derivatives 

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. 

The mixed anhydride method gives more reliable results (33, 44) and is simple, rapid and cheap, especially if a modified process (6) is applied (44). 

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