UDP-N-acetylmuramyl pentapeptide

SA Hitchcock, CN Eid, JA Aikins, M Zia-Ebrahimi, LC Blaszczak. The first total synthesis of bacterial cell wall precursor UDP-N-acetylmuramyl-pentapeptide (park nucleotide). J Am Chem Soc 120 1916-1917, 1998. 

A Lilly group21"3 devised a synthesis of the bacterial cell wall precursor UDP-N-acetylmuramyl-pentapeptide (Park nucleotide) in which deprotection of a 2-(phenylsulfonyl)ethyl ester using a catalytic amount of DBU in dichloro-methane220,221 was an important step in the release of a carboxyl group [Scheme 6,99]. 2-(Methylsulfonyl)ethyl esters have also been cleaved under basic conditions to release a protected carboxylic acid. Scheme 6.100 shows an example from the closing stages of a synthesis of Surugatoxin.222... 

UDP-N-acetylmuramic acid is made from UDP-N-acetylglucosamine (see Figure) on the pathway to synthesis of UDP-N-acetylmuramyl pentapeptide for bacteria cell walls (Figure 16.19, Figure... 

UDP-N-acetylmuramyl pentapeptide is derived from UDP-N-acetylmuramic acid by the sequential addition of the following groups, L-alanine, D-glutamate, L-Lysine, D-Dlanine, D-Alanine (Figure... 

Biosynthesis of bacterial cell wall is remarkable in two respects (1) It entails the synthesis of a regularly cross-linked polymer and (2) Part of the synthesis takes place inside the cell and part outside the cell. The synthesis of cell wall is divided into three stages, which occur at different locations (1) synthesis of UDP-/V-acetylmuramyl-penta-peptide, (2) polymerization of IV-acetylglucosamine and N-acetylmuramyl-pentapeptide to form linear peptidoglycan strands, and (3) cross-linking of the peptidoglycan strands. 

The transfer of the N-acetylmuramyl pentapeptide to phospholipid is reversible and generates a pyrophosphoryl linkage, with one phosphorus atom derived from the lipid and one from the UDP group. That this is so was shown by radioactive labelling of the starting materials and degradation of the product. 

It was found that the first reaction in synthesis of linear peptido-glycan involves the transfer of pentapeptidyl-N-acetylmuramyl 1-phosphate to an endogenous, lipid acceptor from UDP-N-acetyl-muramyl-pentapeptide, with concomitant production of UMP (see Reaction I of Scheme 3). " This reaction is fully reversible, and its kinetics have been studied in detail. Evidence was presented that the glycosyl phosphate is attached to the lipid through a pyrophosphate bridge. Strominger and coworkers found that the endogenous, lipid acceptor could be extracted from the lyophilized. 

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