Rhamnose synthesis

Babaogln K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE. Novel inhibitors of an emerging target in Mycobacterium tuberculosis, snbsti-tnted thiazolidinones as inhibitors of dTDP-rhamnose synthesis. Bioorg Med Chem Lett 2003 13 3227-30. 

A mutant strain of Escherichia coli Y-10, defective in L-rhamnose synthesis, accumulates109 a considerable amount of thymidine diphosphate sugars. Three of them were identified110 as the esters of thymidine 5 -pyrophosphate with 6-deoxy-a-D-xyZo-hexopyranos-4-ulose (28), 6-deoxy-D-glucose, and D-fucose. The fourth component was found to be a 4-acetamido-4,6-dideoxy-D-galactose derivative111,112 (29) it occurs also in Pasteurella pseudotuberculosis102 and its... 

Okazaki, R., T. Okazaki, J. L. Strominger, and A. M. Michelson Thymidine diphosphate 4-keto-6-deoxy-D-glucose, an intermediate in thymidine diphosphate L-rhamnose synthesis in Escherichia coli strains. J. Biol. Chem. 237, 3014 (1962). 

Because of this situation, the prospect of synthesizing D-rhamnosyl cardenolides containing the unnatural, a-D-linkage was investigated. D-Rhamnose has not been reported to occur naturally, but it has been synthesized by Hudson and co-workers (4) in six steps, starting with methyl a-D-mannopyranoside. An intermediate in the synthesis is methyl... 

A more general access to biologically important and structurally more diverse aldose isomers makes use of ketol isomerases for the enzymatic interconversion of ketoses to aldoses. For a full realization of the concept of enzymatic stereodivergent carbohydrate synthesis, the stereochemically complementary i-rhamnose (Rhal EC 5.3.1.14) and i-fucose isomerases (Fuel EC 5.3.1.3) from E. coli have been shown to display a relaxed substrate tolerance [16,99,113,131]. Both enzymes convert sugars and their derivatives that have a common (3 J )-OH configuration, but may deviate in... 

Figure 10.26 Short enzymatic synthesis of L-fucose and hydrophobic analogs, and of L-rhamnose, by aldolization-ketol isomerization, including kinetic resolution of racemic hydroxyaldehyde precursors.

L-Rhamnosone was prepared by the action of hydrochloric acid on L-rhamnose phenylosazone9 and was identified by reconversion to the osazone. This method was later employed186 as a stage in the synthesis of the ascorbic acid analog, L-rhamnoascorbic acid. The benzaldehyde decomposition of the osazone gave a low yield of osone93 and o-nitrobenzaldehyde was not a satisfactory aldehydic substitute. 

A substantial amount of research has been carried out in the field of tetrazole-fused sugars (rhamnose, mannose, and glucose derivatives) - mostly because of the biological importance of these derivatives. In many of these cases synthesis of the fused tetrazole moieties has been perfected by intramolecular 1,3-cycloaddition reactions with participation of a cyano and azido group. Some of these results are shown in Schemes 26 and 27. 

The synthesis of D-mannotetrazole 58 and D-rhamnotetrazole 57 from mannopyranoside 54 (Scheme 3), and L-rhamnotetrazole 59 from L-rhamnose (Scheme 4), provides the first examples of tetrazole analogs of carbohydrates... 

The multi-enzyme system was recently utilized for the synthesis of dTDP-4-keto-6-deoxy-a-D-glucose 3 and dTDP-P-L-rhamnose 5 generating dlTP from dTMP by dTMP kinase and acetate kinase [66, 71]. Further combination with GerB, a dTDP-4-keto-6-deoxy-D-glucose aminotransferase, gave dTDP-4-amino-4,6-dideoxy-D-glucose [72]. 

With carefully selected aliphatic precursors, the synthesis of single stereoisomers of side-chain-substituted pteridines has been achieved (Schemes 20-22). The synthesis of L-biopterin 106 requires 5-deoxy-L-arabinose 102 as a key intermediate preparable from the expensive sugars L-rhamnose and L-arabinose. Alternatively, the readily... 

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