Aldoses, synthesis 2-deoxy

An account of the methods of synthesis of amino sugars has been given in an earlier Volume of this Series1 attention is devoted in this Section to methods recently developed. Several general methods have been employed for the synthesis of 2-amino-2-deoxy-aldoses these respectively involve direct amination of suitable sugar derivatives, interconversion of sugar series, and ascent or descent of a series with or without concomitant amination or molecular rearrangements. 

Synthesis of the 3,4,6-trimethyl ether of 2-deoxy-2-methylamino-n-gluconic acid was carried out along lines similar to those of the synthesis of the 3,6-dimethyl ether. By the addition of methylamine and hydrogen cyanide to 2,3,5-tri-O-methyl-n-arabinose, followed by hydrolysis, only one compound was formed, and this was related to n-glucosamine on the basis of its optical rotation. An attempt to obtain the aldose derivative by reduction with sodium amalgam was not successful, probably because of the impossibility of 5-lactone formation. 

An intriguing and important adaptation of the aldose-nitromethane reaction was also studied in Toronto by Fischer and Jean Grosheintz. By addition of nitromethane to 1,2-0-isopropylidene-n-a 2/fo-pentodialdose and subsequent hydrolysis of the acetone group, they obtained a mixture of 6-deoxy-6-nitro-D-glucose and 6-deoxy-6-nitro-L-idose. A second, intramolecular reaction of these substances led to a mixture of deoxynitro-inositols and, by reduction, to the related aminodeoxyinositols. One of the latter was successfully deaminated a few years later, by T. Posternak, to the B-vitamin, mt/o-inositol (12), thus completing a synthesis of the latter that started from n-glucose. 

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... 

The well known, acid-catalyzed addition of water has been applied successfully in the synthesis of numerous 2-deoxy derivatives of pentoses, hexoses, 6-deoxyhexoses, disaccharides, and methylated aldoses. " ... 

A more general approach to the synthesis of 3-deoxy-ulosonic acids has been presented by Dondoni [82]. The method consisted in the anti-aldol condensation of acyclic aldoses of type 61 with the lithiated 2-acetylthiazole as an equivalent of pyruvic acid to give 62 (Scheme 16). 

The oxidation of aldose phenylosazones to aldos-2-uloses (osones) and the g.l.c. separation of the TMS ethers of the products have been examined in the cases of the D-f/ reo-pentose, D-arabino-, D-lyxo-, L-xy/o-hexose compounds, and two disaccharide derivatives. A new approach to the synthesis of ketonic carbohydrate derivatives involves the treatment of amino-compounds with sterically hindered quinones to prepare imines which rearrange as shown in Scheme 1 to give products which undergo hydrolysis to ketones. The method gave the 2- and 3-ulosides, respectively, when applied to methyl 2-amino-2-deoxy-a- and 3-D-glucopyranoside and methyl 3-amino-3-deoxy-j3-D-allo-furanoside. ... 

Tetroses and Pentoses - 4-0- -Butyldimethylsilyl-2,3-0-isopropylidene-L-threose (1) has been prepared in seven efficient steps from o-xylose. 3,4-0-Isopropylidene-D-eythrulose (4) has been synthesized from the known tetritol derivative 2 by primary protection as the silyl ether 3, followed by Dess-Martin oxidation and desilylation. Compound 2 was derived from D-isoascorbic acid (see Vol. 22, p. 178, refs. 9,10). In a similar reaction sequence, the enantiomer 5 has been obtained from L-ascorbic acid. The dehomologation of several di-0-isopropylidenehexofuranoses e.g., 6- 7) has been carried out in two steps without intermediate purification, by successive treatment with periodic acid in ethyl acetate, followed by sodium borohydride in ethanol. Selective reduction of 3-deoxy-D-g/jcero-pentos-2-ulose (8) to 3-deoxy-D-g/> cero-pent-2-ose (9) has been achieved enzymically with aldose reductase and NADPH." 4-Isopropyl-2-oxazolin-5-one (10) is a masked formaldehyde equivalent that is easily converted to an anion and demasked by mild acid hydrolysis. One of the three examples of its use in the synthesis of monosaccharides is shown in Scheme 1. ... 

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