Aldoses hydrolysis

This reaction was first reported by Kiliani in 1885, and then extended by Fischer in 1889. It is the conversion of an aidose into two one-carbon-higher epimeric homologs, which involves a nucleophilic addition of a cyanide to the terminal carbonyl group of an aldose, hydrolysis of cyanohydrin, and reduction of the resulting lactone. Therefore, it is known as the Kiliani synthesis, Kiliani-Fischer reaction, Kiliani cyanohydrin synthesis, Kiliani-Fischer synthesis, Kiliani-Fischer cyanohydrin synthesis, Fischer-Kiliani cyanohydrin synthesis, or cyanohydrin reaction. This reaction is carried out under alkaline conditions (e.g., at pH > 9.1) to maintain a high effective concentration of cyanide... 

Carbohydrates may be divided into monosaccharides, disaccharides and polysaccharides. The monosaccharides under certain conditions react as polyhydroxy-aldehydes or polyhydroxy-ketones two important representatives are glucose CjHjjO (an aldose) and fructose (laevulose) CgHuO, (a ketose). Upon hydrolysis di- and polysaccharides 3deld ultimately monosaccharides. Common disaccharides are sucrose, lactose and maltose (all of molecular formula C,2H2. 0,), whilst starch, dextrin and cellulose, (CjHjoOj), in which n > 4, are typical polysaccharides. 

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. 

Wolfrom, Sowden, and Lassettre measured the rate of hydrolysis of methylated cellulose in fuming hydrochloric acid at 0°C by continuous mere apt alation of the aldose group formed for each bond ruptured. 

Amino-2-deoxy aldoses. The behaviour of O-unprotected sugars is exemplified in D-gluco series after basic hydrolysis of the starting 2-benzamidoglycoside followed by buffering the medium with carbon dioxide and treatment with thiophosgene, an intermediate isothiocyanate was obtained.320 However, NMR revealed a temperature-dependent equilibrium of this isothiocyanate with a trans-fused OZT (Scheme 5). 

A quite comprehensive study was reported on the enzymatic hydrolysis of zenarestat acyl glucuronide [31]. The major metabolite of the aldose reductase inhibitor zenarestat (11.8) in humans and rats is the acyl glucuronide. This compound was unstable at physiological pH, being converted to its positional isomers and to the aglycone with a global tl/2 value of 25 min at pH 7.4 and 37°. In both rat and human blood, hydrolysis was accelerated by the... 

Reduction of a ketose yields a secondary alcohol, and reduction of an aldose yields a primary alcohol (ccilled an alditol). A possible reducing agent is hydrogenation in the presence of a catalyst, such as platinum another reducing agent is sodium borohydride (NaBH ) followed by hydrolysis. Figure 16-14 illustrates the formation of an alditol. 

Hydrolysis of the diacetamides is effected by acids. Dilute hydrochloric, sulfuric and nitric acid have been used. An aldose with one carbon atom less than the original nitrile is then liberated from the combination. Only exceptionally can this aldose be isolated in pure condition without transforming it into an insoluble derivative in these instances, the method has been employed for preparative work. In most cases the sugar has been characterized as an osazone. The aldose, without great purification, has been employed successfully for reduction - or oxidation experiments. ... 

L-Aldono-1,4-lactones can be prepared from o-aldose perpivaloates and perace-tates (compounds of type 17) [28]. The method implies formation of aldoximes (18), followed by mesylation (Scheme 7). The resulting 5-0-mesyl glyconitrile derivatives (19) are then submitted to acid-catalyzed hydrolysis giving the corresponding 1,4-lactones 20a-c. 

Intramolecular Alkylations. Intramolecular spiroalkylation of the suitably functionalized 5(477)-oxazolone 188 produced 189 in good to excellent yield. Acid hydrolysis of 189 then gave the cyclic amino acid 190 required in the synthesis of the aldose reductase inhibitor sorbinil (Scheme 7.57). ... 

Alkoxy-5,6-dihydro-2/7-pyrans are readily hydrolyzed8889 in dilute, aqueous acids to fnms-a./J-unsaturated aldehydes (206). Hydrolysis in a neutral medium leads to an equilibrium mixture of 5,6-dihy-dro-2ff-pyran-2-ol (207) and the corresponding cis-aldebyde 208. (For syntheses of stereoisomerie deoxy-DL-aldoses from aldehyde 79, see Section II.) The thermal isomerization of 193 has been investigated.1 "... 

In this Section, hydrolysis, acetolysis, and isomerization of acetals are considered. Selective deprotection of acetals may also be achieved through halogenation, hydrogenolysis, ozonolysis, and photolysis, but these topics, are covered in an accompanying article in this Series, on the reactivity of cyclic acetals of aldoses and aldosides,3 and will not be discussed here. 

Of all the selective, deprotection procedures that are available to carbohydrate chemists, the partial hydrolysis of polyacetals is probably the most familiar. Articles by de Beider4,5 and Brady6 contained examples of this type of reaction for aldose and ketose derivatives, respectively, and an article by Barker and Bourne7 gave useful information from the early literature on the graded, acid hydrolysis of acetal derivatives of polyols. A discussion of the stereochemistry of cyclic acetals of carbohydrates was included in an article by Mills 70 and in one by Ferrier and Overend,76 and a survey of the formation and migration of carbohydrate cyclic acetals was made by Clode.7c... 

For a long time, this reaction was conducted exclusively with acety-lated nitriles of aldonic acids, and the products obtained were known in general as "aldose-amides. Fischer2 used this reaction to transform tetra-O-acetyl-L-rhamnononitrile into l,l-bis(acetamido)-l,5-dideoxy-L-arabinitol, whose subsequent hydrolysis and oxidation allowed him to determine the configuration of dextro-tartaric acid (L-threaric acid). 

The reactions enclosed within the shaded box of Fig. 17-14 do not give the whole story about the coupling mechanism. A phospho group was transferred from ATP in step a and to complete the hydrolysis it must be removed in some future step. This is indicated in a general way in Fig. 17-14 by the reaction steps d, e, and/. Step/represents the action of specific phosphatases that remove phospho groups from the seven-carbon sedoheptulose bisphosphate and from fructose bisphosphate. In either case the resulting ketose monophosphate reacts with an aldose (via transketolase, step g) to regenerate ribulose 5-phosphate, the C02 acceptor. The overall reductive pentose phosphate cycle (Fig. 17-14B) is easy to understand as a reversal of the oxidative pentose phosphate pathway in which the oxidative decarboxylation system of Eq. 17-12 is... 

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