Muramic acid derivative

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. 

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). 

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. 

Many derivatives of MDP have been described in which the hydroxyl groups of muramic acid, especially the primary hydroxyl, are substituted in the following only details of the preparation of suitably protected N-acetyl-muramic acid derivatives will be discussed. 

Compound (48), 6-O-mycoloyl-MDP results from acylation of the primary hydroxyl group with natural mycolic acid isolated from mycobacterial cells. Its synthesis is illustrated in Fig. 6 (34, 66). The key intermediate (a), a partially protected N-acetyl-muramic acid derivative, can be substituted by a tosyl group at C-6, which can be exchanged with the potassium salt of the mycolic acid in the presence of 18-crown-6 following the method of Polonsky etal. (58). This mild acylation procedure avoids the use of the acid chloride or trifluoracetic anhydride method, which cannot be applied in the present instance because of the presence of a P-hydroxyl group in mycolic acid. The penta-... 

Treatment of benzyl 2-acetamido-4,6-0-benzylidene-2 deoxy-D-glucopy-ranoside and related muramyl-peptide derivatives with sodium in liquid ammonia removed both the benzyl and benzylidene groups simultaneously, providing a useful alternative to catalytic hydrogenation for glyco-peptides which are catalyst poisons. " Benzyl 2-acetamido-2-deoxy- -D-glucopyrano-side has been converted to the muramic acid derivative (20) which was used to... 

Listowsky and coworkers showed that the c.d. of this sugar derivative is due entirely to lactic acid, and confirmed that this chromophore is in the D configuration for muramic acid. N-Acetylmuramic acid, in which the amino group is replaced by an amido group at C-2, has a c.d. spectrum that is roughly a linear combination of the lactic acid in muramic acid and the amide in 2-acetamido-2-deoxy-D-glucose. This indicates that the amide chromophore and the lactic acid chromophore in N-acetylmuramic acid behave independently. 

The transformation of azidoglucose derivatives into muramic arid precursors enabled the formation of trichloroacetimidates as muramic acid donors that could be very successfully employed in glycoside bond-forma-... 

Kozar, M., and Fox, A. (2002), Analysis of a stable halogenated derivative of muramic acid by gas chromatography-negative ion chemical ionization tandem mass spectrometry, J. Chromatogr., 946, 229-238. 

Sebastian, A., Harley, W., Fox, A., and Larsson, L. (2004), Evaluation of the methyl ester O-methyl acetate derivative of muramic acid for the determination of peptidoglycan in environmental samples by ion-trap GC-MS-MS,/. Environ. Monit., 6,1-6. 

Add (pick) saccharide residues from the list of aldoses (hexoses in al-dopyranose form, pentoses in aldofuranose form, and tetraoses in open-chain form), ketoses (hexoses in ketofuranose form, pentoses and tetraose in open-chain form), derivatives (glucosamine, galactosamine, N-acetylnuraminic acid, N-acetyl muramic acid, inositol, 2-deoxyribose, rhamnose, fucose, and apiose), and blocking groups (H, NH2, =0, COO—, methyl, lactyl, O-methyl, iV-methyl, O-acetyl, iV-acetyl, phosphoric acid, sulfate, iV-sulfonic acid) to build polysaccharides. 

Figure 2 Mode of action of the prototypical lantibiotic nisin. (a) The peptidoglycan precursor lipid II is composed of an N-acetylglucosamine-p-1,4-N-acetylmuramic acid disaccharide (GIcNAc-MurNAc) that is attached to a membrane anchor of 11 isoprene units via a pyrophosphate moiety. A pentapeptide is linked to the muramic acid. Transglycosylase and transpeptidase enzymes polymerize multiple lipid II molecules and crosslink their pentapeptide groups, respectively, to generate the peptidoglycan. (b) The NMR solution structure of the 1 1 complex of nisin and a lipid II derivative in DMSO (6). (c) The amino-terminus of nisin binds the pyrophosphate of lipid II, whereas the carboxy-terminus inserts into the bacterial membrane. Four lipid II and eight nisin molecules compose a stable pore, although the arrangement of the molecules within each pore is unknown (5).

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... 

---