Aldehydo Sugars

A remarkable diastereoselectivity is observed when nitromethane is added to aldehydo sugars of type 7 which carry no oxygen function at C-3 on the a-face13. 

To an ice-cold solution of the aldehydo sugar in CH,OH (ca. 25 mL per g) are added 3 equiv of nitromethane (or nitrocthane), followed by 2.9 equiv of sodium methoxide. After stirring for 2 h 45 min, the medium is neutralized by the addition of acidic Dowex 50, then filtered. Removal of the solvent by distillation and purification by chromatography on silica gel (Ei,0/hcxane) or on aluminum oxide (Et20) furnishes the product yield 85-99%. 

IV-Aldehydes, platinum-group metal catalysts and, 19 621 Aldehydic floral perfumes, 18 357 Aldehydic odor, 3 227t Aldehydo sugars, 4 699 Alder, biomass production by, 17 298-299 Aldgamycins, 15 297t, 298 Aldicarb, 3 777, 778... 

According to Hockett and Chandler, the hydrolysis of an acetylated nitrile (LIII) results in the formation of an acetylated aldehydo sugar (LIV). If this compound then undergoes ammonolysis at carbon atoms 2 or 3, the formation of diacetamides is to be expected, since hemiacetal formation involving the C2 or C3 hydroxyl group is unknown. The... 

Enantiomerically pure nitrile imines (211) have also been generated by the lead tetraacetate oxidation of aldehydo sugar p-nitrophenyl hydrazones. Reaction with methyl acrylate gave the pyrazolines as a 1 1 mixture of the (55) and (5R) epimers, which were resolvable in some cases (116). 

Sterically controlled legiospecific heterocyclization of aldehydo sugars (5-methyl-13,4-triazino[5,6-h]indol-3-yl)hydrazones 116 to 3-(alditol-l-yl)-10-methyl[13>4]triazolo-[4, 3 23][l,2,4]triazino[5,6-b]indoles 117 has been carried out and the antimicrobial activity of some representative memberes tested <99PHA580>. 

The increased yields observed when acylated aldehydo sugars are ammonolyzed was explained on the basis of a greater concentration of the intermediate 96, because the previous stage of ammonolysis of the acyloxy group on C-l is obviated, and, meanwhile, the elimination of the remaining acyl groups as the corresponding amide would be lessened. 

A number of 3-(alditol-l-yl)-5-methyl-7-oxo-l,2,4-triazolo[4,3-a]pyrim-idines l,2,4-triazolo[4,3-a]pyrimidines acyclo C-nucleosides (30) were synthesized (95PHA784) by oxidative cyclization of the corresponding aldehydo-sugar pyrimidin-2-ylhydrazones 27 with bromine in water. The alternative structure 29 was eliminated based on finding that acetylation of 30 afforded the same acetylated acyclo C-nucleosides 31 as those obtained by oxidative cyclization of the (A3-acetyl-poly-0-acetyl)hydrazones 28. Compounds 31 were also obtained by one-pot oxidative cyclization and acetylation of 27. In contrast to the oxidation and concurrent bromination of 19 to 25, it was possible to avoid nuclear bromination of 27 and 28 by performing the reaction in the absence of light (Scheme 13). 

The Sowden homologation [21], based on the nitroaldol condensation (Henry reaction) [22] between the aldehydo sugar and nitromethane in basic medium, followed by the Nef decomposition [23] of the resultant nitronate in strongly acidic conditions, has been employed in a more limited number of cases than the cyanohydrin synthesis. A recent example in this area is shown by the stepwise homologation of (V-acetyl-D-mannosamine (11) into /V-acetylneuraminic acid (12) [24] (Scheme 4). Also, this procedure has found... 

Having set up a protocol for the aminohomologation of various aldehydo sugars, the value of the method was tested by the synthesis of simple natural products. The firsl example involved [57a] the conversion of 2,3 4,5-di-0-isopropylidene-D-arabinose 59 (Scheme 18) through the nitrone 60 into the W-acetyl-D-mannosamine diacetonide 61 and the deprotected compound 11, both well-known key intermediates for the synthesis of /V-acetylneuraminic acid (Neu5Ac) [59,60]. Unfortunately, in this case the addition of 2-LTT (25b) to the nitrone 60 occurred with modest selectivity (ds 75% to the best) therefore, the overall yield of 61 was quite low (29%). 

Fully acetylated aldonic acids can be prepared by oxidation of aldehydo-sugar peracetates. Direct acetylation of certain aldonic acid salts is possible, and addition of cadmium salts, in particular, affords high yields of acetates. The synthesis can also be accomplished by deamination of the readily prepared, acetylated amides with nitrous acid or nitrosyl chloride. Examples of the various methods are given in Ref. 86. 

Samarium(II) iodide promotes comparable transformations of aldehydo sugar 31 to ring contracted product 34 (Scheme 10) [51]. The presences of HMPA and tert-butyl alcohol as a proton source are necessary to obtain good conversion to cyclopentane derivatives. The reac-... 

Decarbonylation of Aldehydo Sugar Derivatives with Chlorotris(methyldiphenyl-phosphine)rhodium(I), D. J. Ward, W. A. Szarek, and J. K. N. Jones, Chem. Ind. (London), (1976) 162-163. 

Application of the Wittig reaction in the carbohydrate field is accompanied by certain difficulties. A correct choice of the initial sugar components is the main problem, owing to the basicity of phosphoranes and, especially, to the drastically basic conditions employed with phosphonium ylides (2a). It is not surprising, therefore, that protected (acetalated and aeetylated) aldehydo sugars and resonance-stabilized phosphoranes were used at first,3-5 although partially protected, and even unprotected, aldoses were shown to be amenable to the reaction with various resonance-stabilized phosphoranes, thanks to the presence of the carbonyl form in the mobile equilibrium. The latter reactions, however, are extremely complicated (see Section IV, p. 284). 

Thus, permethylated aldehydo sugars (6) have been found very susceptible to alkaline conditions, and suffer rapid /8-elimination, because of the acidity of the a-proton, with the formation of the enolic derivative (8) through a possible intermediate anion (7), as shown in equation 2. This phenomenon may explain the absence of interaction17 between the protected dialdose 9 and phenylenedimethylene-bis(triphenylphosphonium) chloride in the presence of lithium eth-oxide. Dialdose 9, indeed, is rapidly transformed18 in an alkaline medium into the unsaturated aldehyde 10 (see also, Ref. 19). Un-... 

More-detailed examination of the reaction between alkylidene(and arylmethylene)triphenylphosphonium ylides and aldehydo sugars was conducted9 8 -30 in our laboratory with 2,3 4,5-di-0-cycIohexylidene-aldehydo-D-xylose (and -L-arabinose), resulting in the preparation of l-C-alkyl-3,4 5,6-di-0-cycIohexylidene-1,2-dideoxy-D-xylo(and L-ara-hino)-hex-l-enitol (27a-27d and 28a-28d, respectivelyB([Pg.236]

Coupling of aldehydo sugars with aroylmethylenetriphenylphos-phoranes affords a practically unlimited source of various 1-C-aryl-a.jS-unsaturated aldoses. p-Substituted 2,3-dideoxy-l-C-phenyl-D-... 

This process of reductive metallation is normally restricted to 2-deoxy sugars in order to avoid a facile P-elimination of the substituent at position 2, usually present in hexoses more relevant to animal systems (e.g., D-glucose, D-mannose). Elimination can be prevented by a protective metallation of the C2 substituent before reductive lithiation at Cl, that is, the production of a dianion, From our experience, these dilithio reagents are not easy to handle and provide only moderate yields when a complex electrophile is used (typically an aldehydo sugar). In 1995, we reported a remarkable and unexpected... 

B. A Radical Route to C-Branched. Aldehydo Sugars An Example in the Synthesis of a-C-Disaccharide... 

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