73089-68-6

Upstream product

• 78246-81-8 benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside 
• 7474-05-7 (R)-2-chloropropionic acid 
• 29617-66-1 (S)-2-chloropropanoic acid 
• 598-78-7 (R,S)-2-chloropropionic acid 
• 1125-88-8 benzaldehyde dimethyl acetal 
• 100-51-6 benzyl alcohol 
• 7512-17-6 N-Acetyl-D-glucosamine 
• 13343-62-9 benzyl 2-acetamido-2-deoxy-α-D-glucopyranoside 

Downstream Products

• 19229-59-5 benzyl 2-acetamido-2-deoxy-3-O--β-D-glucopyranoside 
• 250757-19-8 (R)-2-((2R,4aR,6S,7R,8R,8aS)-7-Acetylamino-6-benzyloxy-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-8-yloxy)-propionic acid 2,2,2-trichloro-ethyl ester 
• 35477-96-4 O¹-benzyl-O⁴,O⁶-(R)-benzylidene-β-muramic acid lactam 

Relevant academic research and scientific papers

Total Synthesis of Dansylated Park's Nucleotide for High-Throughput MraY Assays

The membrane protein translocase I (MraY) is a key enzyme in bacterial peptidoglycan biosynthesis. It is therefore frequently discussed as a target for the development of novel antibiotics. The screening of compound libraries for the identification of MraY inhibitors is enabled by an established fluorescence-based MraY assay. However, this assay requires a dansylated derivative of the bacterial biosynthetic intermediate Park's nucleotide as the MraY substrate. Isolation of Park's nucleotide from bacteria and subsequent dansylation only furnishes limited amounts of this substrate, thus hampering the high-throughput screening for MraY inhibitors. Accordingly, the efficient provision of dansylated Park's nucleotide is a major bottleneck in the exploration of this promising drug target. In this work, we present the first total synthesis of dansylated Park's nucleotide, affording an unprecedented amount of the target compound for high-throughput MraY assays.

Further Insights on Structural Modifications of Muramyl Dipeptides to Study the Human NOD2 Stimulating Activity

A series of muramyl dipeptide (MDP) analogues with structural modifications at the C4 position of MurNAc and on the d-iso-glutamine (isoGln) residue of the peptide part were synthesized. The C4-diversification of MurNAc was conveniently achieved by using CuAAC click strategy to conjugate an azido muramyl dipeptide precursor with structurally diverse alkynes. d-Glutamic acid (Glu), replaced with isoGln, was applied for the structural diversity through esterification or amidation of the carboxylic acid. In total, 26 MDP analogues were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response. Interestingly, MDP derivatives with an ester moiety are found to be more potent than reference compound MDP itself or MDP analogues containing an amide moiety. Among the varied lengths of the alkyl chain in ester derivatives, the MDP analogue bearing the d-glutamate dodecyl (C12) ester moiety showed the best NOD2 stimulation potency.

SYNTHETIC INNATE IMMUNE RECEPTOR LIGANDS AND USES THEREOF

An adjuvant formulation includes a monophosphoryl Lipid A (MPLA) analogue, a Pam3CSK4 analogue, or a muramyldipeptide (MDP) analogue, or combinations thereof. The adjuvant may be formulated in soluble form or in a nanoparticle, such as polylactic glycolic acid nanoparticles. A vaccine formulation comprises the adjuvant formulation and an immunogen. Methods of vaccinating an animal include delivering the vaccine formulation to the animal.

Synthesis of orthogonally protected muramic acid building blocks for solid phase peptide synthesis

Muramic acid is found in many peptide natural products containing oligo(poly)saccharide moieties. Taking into consideration that the Fmoc methodology is routinely used for solid-phase peptide synthesis, preparation of orthogonally protected muramic acid building blocks for total solid-phase synthesis of these natural products is of particular practical importance. Herein a simple and efficient synthesis of benzyl 2-amino-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-N-9-fluorenylmethyloxycarbonyl-α-D-glucopyranoside (6) from N-acetylglucosamine (1) is described. Important improvements over previous synthetic approaches to glucopyranosides 2 (benzyl 2-acetamido-2-deoxy-α-D-glucopyranoside) and 3 (benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside), key building blocks in preparation of 6, include synthesis simplification and efficient isolation and purification. Optically pure (S)-2-chloropropionic acid 7 was prepared and introduced to the positon 3-O of sugar moiety to give compound 4 (benzyl 2-acetamido-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α-D-glucopyranoside) with the (R)-configuration of the lactyl side-chain in excellent overall yield and optical purity. Deacetylation of amino group gave compound 5 (benzyl 2-amino-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α- D-glucopyranoside) suitable for incorporation of the Fmoc protecting group to give protected muramic acid derivative 6, a useful building block in peptide synthesis.

Synthesis of modified peptidoglycan precursor analogues for the inhibition of glycosyltransferase

The peptidoglycan glycosyltransferases (GTs) are essential enzymes that catalyze the polymerization of glycan chains of the bacterial cell wall from lipid II and thus constitute a validated antibacterial target. Their enzymatic cavity is composed of a donor site for the growing glycan chain (where the inhibitor moenomycin binds) and an acceptor site for lipid II substrate. In order to find lead inhibitors able to fill this large active site, we have synthesized a series of substrate analogues of lipid I and lipid II with variations in the lipid, the pyrophosphate, and the peptide moieties and evaluated their biological effect on the GT activity of E. coli PBP1b and their antibacterial potential. We found several compounds able to inhibit the GT activity in vitro and cause growth defect in Bacillus subtilis. The more active was C16-phosphoglycerate-MurNAc-(l-Ala-d-Glu)-GlcNAc, which also showed antibacterial activity. These molecules are promising leads for the design of new antibacterial GT inhibitors.

Synthesis of peptidoglycan units with UDP at the anomeric position

A series of UDP-disaccharide peptide compounds were synthesized as synthetic substrate analogues or potential inhibitors of glycosyl transferase. Fluorescent compounds have been prepared with the aim of developing a screening method for selecting transglycosylase inhibitors.

Synthesis of extended bacterial cell-wall precursor analogues for ligand binding studies with glycopeptide antibiotics

The synthesis of bacterial cell-wall precursor analogues, which resemble the naturally occurring precursor (lipid II) more closely than those hitherto used in NMR binding studies with glycopeptide antibiotics, is reported.