Aldoses 2-deoxy, preparation

The D-glucose/D-mannose system, the most convenient for such model studies, was chosen again however, with the necessary modifications. While 2-C-(hy-droxymethyl)-D-mannose (16 c X = CH2OH, Z = H, n = 2, Scheme 8) is conveniently available via aldolization of 2,3 5,6-di-0-isopropylidene-D-mannose with formaldehyde [50], this is not the case for 2-C-(hydroxymethyl)-D-glucose (15 d X = H, Z = CH2OH, n = 2y Scheme 8). Therefore, both 2-C-(hydroxymethyl) aldoses were prepared by the addition of nitromethane to D-fructose (17) followed by transformation of the intermediates, epimeric l-deoxy-2-C-(hydroxymethyl) alditol-1-nitronates 18 and 19 by the Nef reaction (Scheme 9) [51]. In spite of its apparent simplicity, it was the first synthesis of 2-C-(hydroxymethyl)aldoses using this sequence. Thus, a 1 1 mixture of the branched-chain aldoses 15 d and 16c was obtained in 18% yield. 

In as far as other analytical methods are concerned, many specific reactions have been elaborated for the quantitative determination of 2-deoxy aldoses. 2-Deoxy-D-ribose (2-deoxy-D-erythro-pentose), a compound which was recognized early as playing an important role in biological systems, has been of particular interest. Overend and Stacey (43) have given a critical review of the methods available until 1952 for the estimation of 2-deoxy pentoses. A recent summary of specific methods for the identification and quantitative estimation of the different classes of deoxy sugars has been prepared by Dische (13). 

The initiating reaction between aldoses and amines, or amino acids, appears to involve a reversible formation of an N-substituted aldosyl-amine (75) see Scheme 14. Without an acidic catalyst, hexoses form the aldosylamine condensation-product in 80-90% yield. An acidic catalyst raises the reaction rate and yet, too much acid rapidly promotes the formation of 1-amino-l-deoxy-2-ketoses. Amino acids act in an autocat-alytic manner, and the condensation proceeds even in the absence of additional acid. A considerable number of glycosylamines have been prepared by heating the saccharides and an amine in anhydrous ethanol in the presence of an acidic catalyst. N.m.r. spectroscopy has been used to show that primary amines condense with D-ribose to give D-ribopyrano-sylamines. ... 

Sialic acid aldolase catalyzes the condensation of pyruvate and N-acetylmannosamine to form sialic acid, an acidic sugar involved in a number of biochemical recognition processes. Like other aldolases, sialic acid aldolase accepts a number of aldoses as substrates (12,13). Mannose, 2-deoxyglucose, and many 6-substituted or 6-modified mannose or N-acetylmannosamine, for example, are good substrates for the enzyme. We have prepared 9-deoxy-9-fluorosialic acid and a 7,9-difluoroderivative of sialic acid using sialic acid aldolase as catalyst (Figure 4). In an attempt to prepare 3-deoxy-3-fluorosialic acid, it was found that 3-fluoropyruvate is not a substrate for the enzyme. 

In the Lobry de Bruyn-Alberda van Ekenstein transformation (reviewed by Speck ) of a ketose to the epimeric aldoses, formation of the 3-deoxy-uloses is normally considered to be a side reaction, and both reactions are considered to proceed through a common intermediate, the 1,2-enediol of the sugar. Under the conditions used for preparation of the 3-deoxy-hexos-uloses from the diketose-(amino acids), the former were, however, the main products and the epimeric aldoses only minor products. Furthermore, under these conditions, both reactions were irreversible and the products so stable that the amounts of the two t3rpes of compound were a measure of their rates of formation. The rapid rate of decomposition of the diketose-(amino acids) was probably due to their ready enolization, even in the absence of strong alkali or acid, to give the 1,2-enolammonium compound... 

A further example has been given of the synthesis of a 2-deoxy-aldose by the addition of water to a glycal, but, as this reaction is known to be accompanied by competing eliminations,1 it is being replaced in synthetic work by more-specific addition procedures, for example, methoxymercuration (see p. 210). From the 4-deoxy derivative of D-glucal, prepared by standard procedures from 2,3,6-tri-O-acetyl-4-deoxy-D-xy/o-hexopyranosyl bromide, 2,4-dideoxy-D-threo-hexose was obtained.35... 

Finally, further examples of unsaturated 1-nitroalditols have been described, and have been utilized in standard syntheses of 2-deoxy-aldoses by this means, 2-deoxy-D-rtho-hexose,174 2-deoxy-D-manno-heptose,175 2-deoxy-D-gaiacto-heptose,176 and 2,6-dideoxy-L-manno-heptose177 have been prepared. The reaction of ammonia with 3,4,5,6-tetra-0-acetyl-l,2-dideoxy-l-nitro-L-arabino-hex-l-enitol has been further examined, and found to proceed stereospecifically to give... 

The cyclic acetals have been of great assistance in the preparation of, for example, methylated sugars, - deoxy sugars, and amino-deoxy sugars. The specific syntheses of many di- and tri-saccharides have been described - in these, a suitable acetal of the aldose is caused to react with a poly-O-acetylglycosyl halide or a bromo- or chloro-hydrin derivative. 

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