Synthesis muramyl peptide

VM Titov, EA Meshcheryakova, TA Balashova, TM Andronova, VT Ivanov. Synthesis and immunological evaluation of the conjugates composed from muramyl peptide GMDP and tuftsin. (Z-Thr-ONSu) Int J Pept Prot Res 45, 348, 1995. 

Geert-Jan Boons et al. also synthesized peptidoglycan fragments such as the disaccharide repeating unit [51] and muramyl peptide derivatives containing Lys and DAP residues [52-55] obtained through cross olefin metathesis [56], The muramyl peptides, such as 48 prepared by solid-phase synthesis on Sieber amide resin (Scheme 14.6), were subjected to biological and structural analyses [50, 57, 58] of... 

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. 

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). 

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... 

The lactyl carboxyl group was unmasked by exposure of the phenylsulfonylethyl ester to DBU. Carboxyl group activation of muramic acid derivative 21 was achieved by conversion to the corresponding NHS ester (N-hydroxysuccinimide, EDCI, DMF). The pentapeptide fragment 10 was readily prepared in quantity using standard peptide synthesis protocols [Scheme 7]. Addition of a DMF solution of pentapeptide 10 to a solution of PrNEt2 and the NHS ester deriving from 21 provided the protected muramyl pentapeptide 9 in excellent overall yield. 

In prokaryotic systems bacitracin has been studied much more extensively and several of its effects have been described (see Chapter 3). Bacitracin inhibits the synthesis of mucopeptide in bacteria by preventing the breakdown of undecaprenyl pyrophosphate. This depletes the pool of undecaprenyl phosphate available to act as an acceptor for the transfer of muramyl penta-peptide and so blocks the undecaprenyl phosphate cycle. A similar inhibition... 

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. 

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