Aldoses reduction

The inhibitory activities of 1 l-oxopyrido[2,l-i>]quinazolinecarboxylic acids on rat lens and human placental aldose reductase were studied. From the specific structural and electronic similarities of diverse aldose reductate inhibitors the pharmacophor requirements for an inhibitor were postulated. ... 

A considerable medicinal chemistry effort has gone into devising inhibitors of aldose reductase their inhibition shows a dominant or even exclusive anticompetitive component when measured as inhibitors of aldose reduction, since they form tight complexes of the form E.NAD.I the inhibition is competitive when alditol oxidation is measured. 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Ketose (Section 25 1) A carbohydrate that contains a ketone carbonyl group in its open chain form Kiliam-Fischer synthesis (Section 25 20) A synthetic method for carbohydrate chain extension The new carbon-carbon bond IS formed by converting an aldose to its cyanohydnn Reduction of the cyano group to an aldehyde function com pletes the synthesis... 

Reduction (Section 25.18) The carbonyl group of aldoses and ketoses is reduced by sodium borohydride or by catalytic hydrogenation. The products are called alditols. 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol called an alditol. The reduction occurs by reaction of the open-chain form present in the aldehyde/ketone hemiacetal equilibrium. Although only a small amount of the open-chain form is present at any given time, that small amount is reduced, more is produced by opening of the pyranose form, that additional amount is reduced, and so on, until the entire sample has undergone reaction. 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

Rearrangement reaction, 138 Reducing sugar, 992 Reduction, 229. 348 acid chlorides, 804 aldehydes, 609-610. 709 aldoses, 992 alkene, 229-232 alkyne, 268-270 amides, 815-816 arenediazonium salt, 943 aromatic compounds and, 579-580... 

Aldoses, for example mannose, fucose, arabinose, and others, have been detected at the subpicomole level by their reduction to aldites, which are then transformed into pemaphthoates by means of naphthoylimidazole. These pemaphthoates show strong fluorescence at 374 nm, and can be easily separated by HPLC.[46]... 

In clinical chemistry however, these systems have not been differentiated as yet. Since the oxidation of an alcohol corresponds to the reduction of a ketose or an aldose, the designations ketose reductase and aldose reductase, respectively, were suggested (H4, W14). In this paper however, the enzyme or enzyme system will be named polyol or sorbitol dehydrogenase (SDH), although the latter expression does not characterize exacdy the enzyme s function in a general biochemical sense. But sorbitol or fructose have been commonly used as substrates in clinical chemical investigations. 

Anhydroalditols can be easily generated by Lewis acid catalysed reduction of the corresponding aldoses or glycosides with triethylsilane (Fig. 2). The reaction requires protection of the hydroxyl groups, which can be performed temporarily by preliminary treatment with bis(trimethylsilyl)-trifluoroacetamide (BSTFA).1... 

VIII. Reduction of Aldonolactones 1. Reduction to Aldoses and Alditols... 

Isotopic Labeling and Substitution at the Anomeric Center of Aldoses by Reduction of Aldonolactones... 

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