186770-33-2

Upstream product

• 40429-51-4 1,2-O-isopropylidene-5-O-toluene-p-sulphonyl-β-D-arabinofuranose 
• 6773-29-1 dimethyl diazomalonate 

Downstream Products

• 178426-25-0 2-[(3aS,5R,6R,6aS)-2,2-Dimethyl-5-(toluene-4-sulfonyloxymethyl)-tetrahydro-furo[2,3-d][1,3]dioxol-6-yloxy]-acrylic acid methyl ester 

Relevant academic research and scientific papers

First nonenzymatic synthesis of Kdo8P through a mechanism similar to that suggested for the enzyme Kdo8P synthase

The mechanism of Kdo8P synthase, the enzyme that catalyzes the unusual condensation of D-arabinose 5-phosphate (A5P) with phosphoenolpyruvate (PEP) to form Kdo8P, remains a fascinating subject for bioorganic research. This paper describes the synthesis of two intramolecular models (1 and 2) bearing an enolpyruvate moiety at C-3 of the arabinose fraction. This means that their open-chain aldehyde forms closely mimic the proposed situation, whereby two substrates A5P and PEP evolve into a ternary complex with the synthase. Examination of 1 (in organic solvent) and 2 (in a water solution) under Lewis acid conditions establishes that they both undergo highly stereospecific intramolecular condensation of the enolpyruvate double bond with the carbonyl of sugar. This results in the required Kdo structure possessing the desired stereochemistry. Mechanistic studies suggest that the observed intramolecular condensation process takes place via a stepwise mechanism involving the formation of a transient oxocarbenium ion intermediate. The results obtained, uniquely demonstrate enzyme-like chemistry in the stereospecific synthesis of the Kdo system. Further investigation is certainly warranted, in order to facilitate the construction of other 3-deoxy-2-ulosonoc acids and sialic acids on the basis of the same general model. This is illustrated here in the case of Kdo. Furthermore, the results support the validity of the mechanism suggested for the Kdo8P synthase action, in particular, the possible role of the enzyme in the catalysis of the initial condensation step.

A new model for the stereoselective construction of the Kdo structure through a mechanism similar to that suggested for the enzyme Kdo8P synthase

Stereospecific chemical synthesis of the Kdo structure was demonstrated using a mechanism similar to that suggested for the enzyme Kdo8P synthase. The derivative of D-(-)-arabinose (compound 3), in which the enolpyruvate moiety is attached at C-3 hydroxyl, was synthesized in 12 chemical steps and an intramolecular condensation of enolpyruvate and aldehyde functions was examined, under Lewis acid conditions.