Octulosonic acid, 3-deoxy-, esters with

Carbohydrate lactones have been used as the carbonyl reagent in the Reformatsky reaction. Thus, 2,3 5,6-di-O-cyclohexylidene-D-mannono-1,4-lactone [44, obtained by oxidation of the mannofuranose derivative (49)] reacted with ethyl bromoacetate and zinc to give the protected 2-deoxy-3-octulosonic acid ethyl ester (45a) in 69% yield (50). Ketonic hydrolysis with potassium hydroxide in aqueous methanol, followed by acidification and heating, afforded the 1-deoxyheptulose derivative 45b. Similarly, starting from compound 44, the 1-C-substituted allyl and propar-gyl lactols were prepared on reaction with allyl or propaigyl bromides in the presence of zinc (51). 

The occurrence of 3-deoxy-D-manno-octulosonic acid in lipopoly-saccharides has prompted its synthesis,537 together with the D-gal-octo158 and the D-gluco analogs.157 Although gas-liquid chromatography was successfully used to analyze the products of these syntheses, it has been reported that methanolysis of a bacterial endotoxin lipopolysaccharide failed to yield 3-deoxy-D-manno-octulosonic acid, presumably because of the lability of the latter to acid.381 However, Kasai and Nowotny have reported four peaks for the O-trimethylsilyl derivatives of 3-deoxy-D-manno-octulosonic acid obtained by methanolysis of the glycolipid from a Salmonella minnesota mutant.538 Reduced 3-deoxy-D-manno-octulosonic acid and its methyl ester have also been analyzed successfully as their acetates.339,539... 

Methyl glyoxylate dithioacetal 292, after lithiation, reacted with a protected D-mannitol triflate in the presence of HMPA. This methodology has been applied to the synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO)462. A related ethyl glyoxylate dithioacetal 293 gave conjugate addition to different Michael acceptors, such as a,fi-unsaturated esters, lactones and lactams463,464. 

By an analogy to the radical syntheses above, the carbon chain elongation reaction was achieved by Barton et al. [109] in the reaction with ethyl a-trifluoroacetoxy acrylate 165. Under radical conditions 165 was coupled with the ester 164 prepared from pentaacetyl gluconic acid and /V-hydroxy-2-thiopiridone (Scheme 35) to afford an unstable intermediate 166, readily convertible to the unsaturated a,p-keto acid 167. The methoxymercuration-demercuration of 167 gave a low selectivity, providing the mixture of 3-deoxy-4-methoxy-D-man/jo and D-g/wco-octulosonic acids (4 3) in a moderate yield [110]. 

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