L,2:5,6-Di-O-isopropylidene-a-D-glucofuranose

Carbohydrate derivs. Aq. KCN added dropwise at 0 to a well-stirred mixture of l,2 5,6-di-0-isopropylidene- a-D-r/Z>o-hexofuranosul-3-ose hydrate and NaHCOg in ethanol-water 3-C-cyano-l,2 5,6-di-0-isopropylidene-a-D-allofuranose (Y 90%) stirred vigorously at room temp, in aq.-alc. KCN for 18 hrs. -> 3-C-cyano-l,2 5,6-di-O-isopropylidene-a-D-glucofuranose (Y 80%). - The allo-isomer is obtained under kinetic control, the gluco-isomer under thermodynamic control. J.-M. Bourgeois, Helv. 58, 363 (1975). 

Of particular value, was the reagent s ability to oxidize a hydroxyl group attached directly to a furanoid ring (6, 7, 46), as is illustrated by the conversion of l,2 5,6-di-0-isopropylidene-a-D-glucofuranose into l,2 5,6-di-0-isopropylidene-a-D-n o-hexofuranos-3-ulose (1). The follow-... 

Acetalation. As polyhydroxy compounds, carbohydrates react with aldehydes and ketones to form cyclic acetals (1,13). Examples are the reaction of D-glucose with acetone and a protic or Lewis acid catalyst to form l,2 5,6-di-0-isopropylidene-a-D-glucofuranose [582-52-5] and its reaction with benzaldehyde to form 4,6-O-benzylidene-D-glucopyranose [25152-90-3]. The 4,6-0-(l-carboxyethylidine) group (related to pyruvic acid) occurs naturally in some polysaccharides. 

Chlorodeoxy sugars have been reduced [15] also with lithium aluminum hydride. In one experiment, 3-deuterio-l,2 5,6-di-0-isopropylidene-a-D-allofuranose was converted into 3-chloro-3-deoxy-3-deuterio-l,2 5,6-di-0-isopropylidene-a-D-glucofuranose by treatment with triphenylphosphine-carbon tetrachloride reduction with lithium aluminum hydride gave 3-deoxy-3-deuterio-1,2 5,6-di-0-isopropylidene-a-D-ro-hexofuranose with retention of configuration at C-3. 

The syntheses of the thymine nucleosides of 2,4-dideoxy-p-D-eryt/zro-hexo-pyranose starting from l,2 5,6-di-(9-isopropylidene-a-D-glucofuranose (12 steps) or from tri-O-acetyl-D-glucal (11 steps) have been reported.250... 

Oxidation of l,2 5,6-di-0-isopropylidene-a-D-glucofuranose (217) with ruthenium tetraoxide, using a phase-transfer catalyst, gave the 3-ulose derivative 218, which by further hydrolysis afforded D-n Zw-hexos-3-ulose 219. Benzyltriethylammonium chloride (BTEAC) was used as the catalyst. Using the same oxidant and conveniently derivatized starting materials, a-D-xy/o-hexofuranos-5-ulose, a-D-n Zw-hexofuranos-5-ulose, and /f-L-arabino-hexofuranos-5-ulose derivatives were obtained.436... 

In addition to the sulfonyloxy displacement reaction which may occur on halogenation with triphenyl phosphite complexes, the possibility of acetal migration (with appropriate structure) should not be overlooked. Thus, 1,2 5,6-di-O-isopropylidene-a-D-glucofuranose with triphenyl phosphite dibromide in benzene for 48 hours afforded " (presumably) 6-bromo-6-deoxy-l,2 3,5-di-O-isopropylidene-a-D-glucofiiranose, which was hydrolyzed to 6-bromo-6-deoxy-D-glucose in 10% overall yield. In some compounds, steric factors may prevent the introduction of halogen. With vicinal glycols and triphenyl phosphite methiodide, phosphonic ester formation occurs instead of halide production, but this reaction may be eliminated by use of triphenylphosphine in carbon tetrachloride. 

However, some limitations in the application of this halogenation procedure have been noted. For example, l,2 5,6-di-0-isopropylidene-a-D-glucofuranose 40, in which C-3 is sterically hindered, gives the 5,6-acetal rearranged product 41 (O Scheme 25) [42]. 

The 4,5-unsaturated pyranoses or 3,4-unsaturated furanoses are usually prepared by a base-catalyzed elimination of a leaving group such as halogen, sulfonyloxy etc. from appropriate sugar derivatives. The classical example is represented by the synthesis of compound 19 from l,2 5,6-di-0-isopropylidene-a-D-glucofuranose 18 [1]. Analogous elimination performed for 20 led to derivative 21 from which capuramycin—a complex nucleoside antibiotic could be prepared readily (O Scheme 14) [30]. 

A method for the separation of acetals from the parent hydroxylated compounds has been described by Barnett and Kent. Paper made of cellulose acetate was used with 3 2 (v/v) methanol-water for separation, and zones were detected either with (2,4-dinitrophenyl)hydra-zine or with acidified potassium permanganate. The limit of detection (of l,2 5,6-di-0-isopropylidene-a-D-glucofuranose) is about 150 ixg. Later, Bird introduced the combination of ceric ammonium nitrate and silver nitrate sprays as detection reagents specific for acetals of carbohydrates. By this technique, the limit of detection (of 1,2 5,6-di-O-isopropylidene-a-D-glucofuranose) is 8-12 fig,... 

Irvine and Scott found that the mono-O-methyl-D-fructose obtained by methylation of a -di-0-isopropylidene-D-fructose and subsequent hydrolytic removal of the acetone groups gave the same mono-O-methyl-D-hexulose phenylosazone as that obtained by methylation of l,2 5,6-di-0-isopropylidene-a-D-glucofuranose, hydrolytic cleavage of the acetone residues, and formation of the phenylosazone. Further evidence for the structures of these two diacetals was obtained when Karrer and Hurwitz showed that each was unaffected... 

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