Ulosonic acid synthesis alternative approach

An alternative approach to the stereocontrolled synthesis of ulosonic acids was based on nucleophilic acylation of 2,3 5,6-di-O-isopropylidene-D-mannose 173 with a glyoxylate carboanion [116] derived from the mercaptal glyoxylate (Scheme 37). As a result the corresponding thio-octulosonates 174 and 175 were formed in 76% yield. Both compounds were converted to 176 using NIS (or NBS) and then MeONa. Applying Barton procedure [117] 176 was deoxygenated at C-3 to afford KDO derivative 124. 

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. 

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