Fructose cyclic acetals

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... 

Condensation of D-fructose with dry acetone or benzaldehyde affords cyclic acetals. The same procedure with cyclopentanone, with concentrated sulfuric acid as the catalyst and stirring at room temperature for some 40 hours, gave a sirupy product which was characterized by its p-tolylsulfonyl derivative. Cyclohexanone yielded a crystalline product of m.p. = 142°, readily isolated and purified. For the acetal, structure... 

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. 

Zervas and Sessler synthesized an isomeric mono-O-isopropylidene-D-fructose by acetonating 1,6-di-O-benzoyl-D-fructose, prepared by treatment of D-fructose cyanohydrin with two molar proportions of benzoyl chloride in the presence of pyridine. The cyclic acetal obtained after debenzoylation was named 2,3-acetone-a-D-fructo-furanose by the authors, although, quite evidently, it is 2,3-0-isopropylidene-j8-D-fructofuranose (90). 

Miethchen and co-workers have published a number of papers concerning the use of chloral and dicyclohexylcarbodiimide (DCC) as a means to invert configuration of chiral centres in carbohydrates. These reagents were found to react with his-vicinal triols with a cis, trans sequence of hydroxyl groups and this resulted in the formation of cyclic acetals in which the central atom of the triol had been inverted. For example, the rare monosaccharide o-tagatose has been easily prepared from D-fructose (Scheme 4) [6]. Concerning the mechanism of this reaction, chloral and DCC react with fructose derivative 10 to give intermediates 11 and 12. The latter mentioned intermediate then reacts intra-molecularily in an SN2-type reaction as shown. This furnished product 13 in 59% yield. 

Although the IUPAC has dropped the term ketal for the acetal of a ketone, most carbohydrate chemists still use the term. Therefore, the cyclic hemiacetal of fructose is often called a hemiketal. 

A most important theoretical study was presented by Hennig on the possible reaction-mechanisms involved in the formation of cyclic and keto derivatives during acetylation (see Scheme III). When 1 mole of 3,4,5-tri-0-acetyl-l,6-di-0-trityl-fcefo-D-fructose (a) is treated at room temperature with two moles of acetyl bromide in acetic anhydride, 1,3,4,5-tetra-... 

The My values for n-glucosone and its dimethyl acetal have already been discussed (see p. 272). In contrast to the migrations of the aldoses studied and, in particular, to the strong tendency of the cyclic keto carbohydrates to form addition products with hydrogen sulfite, n-fructose and other hexuloses and pentuloses studied showed no migration. This is probably mainly due to steric hindrance analogous to the reluctance of aliphatic ketones to form addition products with hydrogen sulfite (as compared with the behavior of aldehydes or cyclic ketones). 

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