2- Deoxy-ulosonic acid analogues

Analogous cycloaddition reaction of sodium glyoxylate, in water, onto penta-2,4-dienol has been used for synthesis of seven carbon 2-deoxy-ulosonic acid analogues as depicted in Scheme 56 [145]. 

Such an important biological and immunological role of 3-deoxy ulosonic acids, as well as their unique chemical structure has emerged as an important area of many research fronts. Much attention has been also focused on enzymatic, chemoenzymatic, and stereocontrolled chemical syntheses of all of these compounds and their analogues. 

All previously described approaches to 3-deoxy-2-ulosonic acids started from advanced carbohydrate precursors, and thus they are not easily applicable to the synthesis of structurally diverse analogues. This concerns chemical syntheses relying on sugar-derived stereocenters and enzymatic ones, providing only very limited access to some naturally occurring compounds. In contrast, de novo syntheses starting from simple, achiral compounds offer much more flexible alternative approaches to synthesis of unnatural ulosonic acid analogues. 

The stereochemical outcome of the hetero Diels-Alder reaction of the erythrose based diene with sodium glyoxylate was further rationalized by preparing the same compounds via decarboxylation of 2-carboethoxy-2-deoxy-2-ulosonic acid esters, obtained by cycloaddition with diethyl ketomalonate [146], A range of 2-nonulosonic acid derivatives - KDN analogues - were prepared including protected form of 2-deoxy-KDN,... 

An enantioselective synthesis of 18 was achieved. This is a deoxy analogue of naturally occurring 3-deoxy-D-gf/yccro-D-firu/acm-2-non-2-ulosonic acid (KDN). ... 

A route to hept-2-ulosonic acid derivatives is available by way of the reaction of 2,3 4,5-di-0-isopropylidene-L-arabinose and 2,4 3,5-di-0-ethylidene-L-xylose with ethyl nitrosoacetate. ° Isomerization of the intermediate nitroso derivatives with alcoholic sodium nitrite yielded the corresponding oximes, which can be deoximated with lead tetra-acetate in acetic acid. 3-Deoxy-D-manno-oct-2-ulosonic acid 5-(dihydrogen phosphate) and its D-gluco analogue have been obtained by base-catalysed condensation of o-arabinose 2-phosphate (obtained by way of phosphorylation of benzyl 3,4-0-isopropylidene-P-D-arabinopyrano-side) with oxalacetic and separation of the isomers by ion-exchange chromato-graphy. ... 

The phosphonate analogue of cytldine 5 -monophospho-3-deoxy-D-manno-oct-2-ulosonic acid has been synthesized as illustrated in Scheme 14, and "azacyclic-2-deoxy-KDO" was produced from KDO as shown in... 

The anhydroribonlc acid derivative (12) has been prepared from isopro-pylidene-D-glyceraldehyde.ib Several 8-substituted analogues (13) of 2-deoxy-P-KDO have been prepared and shown to be inhibitors of CMP-KDO synthetase, although they did not display antibacterial activity. A number of similar 2-deoxy compounds are discussed together with their ulosonic analogues in the next section. 

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