Ketoses cyclic acetals

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... 

Study of this reaction has not been limited to cyclic acetals of aldoses and aldosides, and synthetic applications in the ketose series have been developed,273,276,278,278 particularly for isopropylidene acetals of D-fructose. As an illustration of these reactions, two examples are given here. The action of butyllithium on 2,3 4,5-di-0-isopropyli-dene-l-0-methyl-/3-D-fructopyranose (280) gave273 a 30% yield of the 5-enopyranose 282. Abstraction by the base of the axial hydrogen atom from the 6-methylene group, giving the anion 281, was invoked... 

Several reviews have already been published on the subject, for example, the acetala-tion of alditols [4], of aldoses and aldosides [5,6], and of ketoses [7]. Some aspects of the stereochemistry of cyclic acetals have been discussed in a review dealing with cyclic derivatives of carbohydrates [8], also in a general article [9] and, more recently, in a chapter of a monograph devoted to the stereochemistry and the conformational analysis of sugars [10], Aspects on predicting reactions patterns of alditol-aldehyde reactions are reviewed within a general series of books on carbohydrates [11]. The formation and migration of cyclic acetals of carbohydrates have also been reviewed [12,13],... 

Dialkyl dithioacetal derivatives of ketoses, such as D-fiuctose and L-sorbose, me inaccessible directly from the parent sugars, the ketose undergoing extensive decomposition under the conditions employed for mercaptaladon of aldoses. Such derivatives can, however, be prepared by indirect methods. Acetylation of D-fiuctose [40] and L-soibose with acetic adiydride and zinc chloride [41] leads to good yields of acyclic pentaacetates in which foe ketose carbonyl is not involved in a cyclic acetal. Subsequent treatment of these acetylated derivatives with thiols affords foe acetylated dialkyl dithioacetals in satisfactory yields, and conventional deacetylation affords foe unprotected dialkyl dithioacetals [40,41]... 

In base, aldoses and ketoses rapidly equilibrate to mixtures of sugars (Fig. 123) (174). Most sugars react with alcohols under acidic conditions to yield cyclic acetals (glycosides). Glycoside formation, like acetal formation, is catalyzed by acid and involves cation intermediates (Fig. 124). 

Methods in Structural Polysaccharide Chemistry, 15, 53-89 Brady, Robert F., Jr., Cyclic Acetals of Ketoses, 26, 197-278 Bray, H. G., D-Glucuronic Acid in Metabolism, 8, 251-275... 

R. R Brady, Jr., Cyclic acetals of ketoses, Adv. Carbohydr. Chem Biochem 26 197 (1971). J. A. Mills, The stereochemistry of cyclic derivatives of carbohydrates, Adv. Carbohydr. Chem 10 1 (1955). 

Review of cyclic acetals and ketals of ketoses R. F. Brady, Adv. Carbohydr. Chem. Biochem., 1971, 26, 197. 

Cyclic acetals of ketoses are important and useful compounds. Among other applications, they can be used as intermediates in the synthesis of numerous, useful sugar derivatives and as substrates for studies of conformational principles in fused-ring, heterocyclic A personal contribution by the author. 

General reviews on cyclic acetals of carbohydrates have appeared. The cyclic acetals of the aldoses and aldosides have been treated in this Series by de Beider, but inclusion of cyclic acetals of ketoses was beyond the scope of his Chapter. Other articles, by Barker and Bourne, Mills, and Ferrier and Overend, have been concerned with the stereochemistry and conformation of cyclic acetals of the carbohydrate group. The purpose of the present article is to supplement de Beider s Chapter with a description of the pertinent original work, optimal laboratory preparations, properties, and applications of the cyclic acetals of ketoses, and to provide a summary of the known theoretical aspects of their formation, rearrangement, and hydrolysis. 

Emil Fischer first described the condensation of D-fructose with acetone in 1895, and most of the early work on cyclic acetals of ketoses was performed with D-fructose. In 1934, Reichstein and Griissner published their classic synthesis of L-ascorbic acid (vitamin C), in which L-sorbose was converted into 2,3 4,6-di-0-isopropylidene-a-L-sorbofuranose or other di-alkylidene acetals. The emphasis of research activity then shifted to L-sorbose, and to the elucidation of an optimal procedure for preparing such diacetals. At about the same time, Levene and Tipson used isopropylidene acetals as derivatives for the purification of L-cri/thro-pentulose (as the di-isopropylidene acetal) and D-thrco-pentulose (as the monoisopropyli-dene acetal). Soon thereafter, Reichstein and coworkers used diisopropylidene acetals of D- and L-psicose, and D-tagatose, to purify the respective sugars. 

Cyclic acetals of ketoses are prepared most commonly from acetone or benzaldehyde formaldehyde, acetaldehyde, butanone, and cyclohexanone have been used occasionally. These carbonyl reagents are frequently used directly, although such derivatives as 2,2-di-methoxy- or 2,2-diethoxy -propane (acetone dialkyl acetals), or l,l-dimethoxyethane (acetaldehyde diethyl acetal), are often employed in experiments in which intermediate acetals are of interest,or in which the presence of water in the reaction mixture adversely affects the yield of products. A polymeric form of an aldehyde is the reagent to be preferred whenever the monomer is volatile for example, acetaldehyde is often used in the form of a trimer, paraldehyde, and formaldehyde is employed as formalin solution, as paraformaldehyde, or as polyoxymethylene. An excess of the carbonyl reagent is generally used as the solvent, and the condensation is usually effected at room temperature. 

De Beider has reviewed the stability of cyclic acetals of the aldoses and aldosides to heat, light, bases, and oxidants and reductants. His Chapter gives many examples of the kinds of reactions that may be expected to occur when cyclic acetals of ketoses are subjected to such conditions. 

The acid-catalyzed hydrolysis of cyclic acetals of ketoses is best effected by use of 0.1 M aqueous oxalic acid or 50-80% aqueous acetic as the hydrolyst, because the use... 

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