Muramic acids, synthesis

UDPG was the first of a whole new class of nucleotides, in which the uridine diphosphate group is attached to a monosaccharide. Two important members of the class are uridine diphosphate glucuronic acid, the intermediate in the synthesis of glucuronides and of many other compounds, and uridine diphosphate N-acetylglucosamine which is an intermediate in the synthesis of mucopolysaccharides. Uridine diphosphate muramic acid was isolated by Park (P2) from Staphylococcus aureus... 

Purification of some enzymes participating in the biosynthesis of glycopeptide cell-wall precursors has also been achieved. Examples include preparation of the enzymes necessary for synthesis of the enol ether 38 (see Section 11,6, p. 328),152-153-450 reduction of the enol ether to the muramic acid derivative,152-450,451 and the addition to the latter of amino acids452-456 or the dipeptide D-alanyl-D-alanine.160-457-458... 

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. 

The synthesis of this substance, starting with methyl 2-acetamido-4,6-0-benzylidene-2-deoxy-a-D-glucoside, was performed as follows. The two isomers which were formed were separated on a Dowex 50 colunm, and one (Md +109°) was shown to be identical with natural muramic acid. The strong dextrorotation effectively ruled out the L-glucosamine configuration, and the configuration of the lactic moiety was deduced to be most likely d. The second isomer had [ ] +52° and differed, in its behavior on resin columns and in paper chromatography, from natural muramic acid. 

In the synthesis of branched glycopeptide, the resin-bound compound 50 was obtained through a series of steps using standard coupling chemistry (PyBOP, HOBt, DIEPA), Fmoc-protected amino acids, starting from Fmoc-D-Ala, and a suitably protected NAM derivative (2-7V-acetyl-l- 0-allyl-4,6-benzylidene-3-muramic acid) at the end (Figure 6). Dotted arrows indicate the... 

In 1995 Nicolaou and coworkers initiated a renaissance in the construction of sugar amino acid conjugates with their synthesis of carbonucleotoids [49]. Although they did not prepare amide-linked carbohydrates, they did introduce the term carbopep-toid to designate such materials. Shortly thereafter, a number of papers directed toward the synthesis of carbopeptoids appeared. One of the earliest was reported by Wessel et al., who used nor-muramic acid derivatives and condensed them in solution by means of 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT) in DMF to construct a tetramer (Fig. 27). 

Another application of alkoxylation of nitro-olefins is in the synthesis of positional isomers of muramic acid.156 Addition of isopropyl L-lactate or isopropyl D-lactate to 141 led to the side-chain epimers 199 and 200, respectively, in yields of over 80%. When isopropyl dl-lactate was used, 199 and 200 were obtained as a mixture in which, interestingly, the former preponderated. Removal of protecting groups, reduction, and derivation furnished various derivatives of 3-amino-2-0-[D(and L)-l-carboxyethyl]-3-deoxy-D-glucose (201). 

The synthesis of peptidomimetics based on a D-glucose or D-allose scaffold featured 2,3-di-0-alkyl-6-0-aryl-4-0-carboxymethyl-pyranose compounds/ while a muramic acid analogue has been used in the solid phase synthesis of peptido-glycan monomers for the generation of a combinatorial library/... 

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