Glucose derivatives, preparation

D-glucose derivative prepared from the reaction of labelled acetyl... 

Metal halide salts other than sodium iodide have been used sparsely to prepare halodeoxy sugars from sulfonate esters. Lithium chloride (107) and lithium bromide (33) have found limited application. Potassium fluoride (dihydrate) in absolute methanol has been used (51, 52) to introduce fluorine atoms in terminal positions of various D-glucose derivatives. The reaction is conducted in sealed tube systems and requires... 

For the synthesis of D-glucuronic acid, methods of oxidation of suitable D-glucose derivatives have been devised during the past two decades these procedures have been comprehensively reviewed by Marsh,6 Mehltretter,7 and Heyns and Paulsen.8 For special purposes, for example, for the preparation of 6-I4C-labelled D-glucuronic acid, chain-extension reactions of 1,2-O-isopropylidene-a-D-xy/o-pen-todialdo-I,4-fiiranose by the cyanohydrin synthesis9 or by ethynyla-tion10 are used, but these frequently yield mixtures of D-glucuronic acid and L-iduronic acid. 

Scheme 5.73 Selective preparation of 2-substituted glucosides via 1,6-anhydro-D-glucose derivatives.

The final example (Scheme 5.73) illustrates the efficient preparation of epoxide 212 from 2-iodo-l,6-anhydro-D-glucose 67 (see Scheme 5.5) [221,222]. This Cerny epoxide [109] is a useful and versatile precursor to a range of 2-substituted glucose derivatives 213, which can be elaborated further to suitable glycosyl donors. 

Proof of Constitution.—Irvine and his school20,160,163 were not slow to recognize that the new trimethylglucose, prepared by them from iso-propylidene-D-glucose, a compound not then characterized, differed from the normal series of glucose derivatives in the extreme ease of its oxida-... 

Historically, techniques such as the formation of osazones and the demonstration of fermentation have contributed significantly to the separation and identification of carbohydrates. Observation of the characteristic crystalline structure and melting point of the osazone derivative, prepared by reaction of the monosaccharide with phenylhydrazine, was used in identification. This method is not completely specific, however, because the reaction involves both carbon atoms 1 and 2 with the result that the three hexoses, glucose, fructose and mannose (Figure 9.19), will yield identical osazones owing to their common enediol form. 

Park et al." used U-4CR libraries to prepare Ras-Raf protein-binding compounds like 30 that are active against HIV. The patented product 31 has been formed by Lockhoft at the Bayer AG using a U-4CR of four different protected glucose derivatives that were later deprotected. The product 32 of... 

The dioxirane epoxidation of a prochrral alkene will produce an epoxide with either one new chirality center for terminal alkenes, or two for internal aUcenes. When an optically active dioxirane is nsed as the oxidant, expectedly, prochiral alkenes should be epoxi-dized asymmetrically. This attractive idea for preparative purposes was initially explored by Curci and coworkers in the very beginning of dioxirane chemistry. The optically active chiral ketones 1 and 2 were employed as the dioxirane precursors, but quite disappointing enantioselectivities were obtained. Subsequently, the glucose-derived ketone 3 was used, but unfortunately, this oxidatively labile dioxirane precursor was quickly consumed without any conversion of the aUcene . After a long pause (11 years) of activity in this challenging area, the Curci group reported work on the much more reactive ketone... 

In work on enzymic deacetylation, a series of D-glucose derivatives acetylated at specific positions was prepared, and the O-trimethylsilyl derivatives of these D-glucose acetates were separated by gas-liquid chromatography.352,353 Research on bacterial glycolipids required the characterization of 3- and 6-O-palmitoyl-D-glucose, the separation of which, as their O-trimethylsilyl and acetyl derivatives, was studied.354... 

The association between Drs. Fletcher and Pravdic, which started when she was a Visiting Scientist at the Institute in Bethesda, continued after she returned to Yugoslavia. Together they investigated the chemistry of unsaturated 2-acetamido-2-deoxy-D-glucose derivatives, and, with Emmanuel Zissis, the preparation of lactones from these sugars, work stemming from Dr. Fletcher s interest in Tay-... 

As with epoxides, carbanions can add in a 1,4 fashion to enones or nitrosugars. Nitromethane anion has been used [64], Dithiane anion has been successfully used in the addition to nitroolefins [65] and to enones [66], Accordingly, C-5 branched-chain glucose derivatives 47 and 48 have been prepared from nitroolefin 46 (Scheme 20) [67,68], Sugar-derived enones have been also used as acceptors in free radical reactions to trap alkyl radicals as well as anomeric radicals (see Schemes 29 and 30). 

Figure 4. Gas chromatogram of TMSi derivatives prepared from an aqueous equilibrium solution of glucose and galactose. The column was 2.5% SE-30, isothermal at 160°. Gal = galactose glu = glucose.

Dithioacetals have also been used as precursors for the transacetalization. Thus, both diastereomers 213 and 214 have been prepared from glucose-derived dithioacetal 212 and rac-230 and used for the efficient resolution of rac-Y)l (Scheme 60) <1995TA295>. 

It has been reported that some simple, synthetic glycollpids, such as II-fatty acylated 2-amino-2-deoxy-D-glucose derivatives, exhibit potent immunostimulatory activities (5). We first examined a facile preparation of N-fatty acylated 2-amino-2-deoxy-D-glucopyranosides, which would be key intermediates for the synthesis of lipid A and its analogs (Figure 2). For this purpose, the one-step glycosylation catalyzed by ferric chloride (6, 7) was employed. 

Takahashi et al.45 used a 4-hydroxybenzenesulfonate linker on Syn-Phase polystyrene Crowns to prepare glucose derivatives and macrocycles (Scheme 20). Displacement of the monosaccharide-supported Crowns 70 with nucleophiles such as azide, iodide, and acetate gave the respective 6-substituted glucose derivatives 71, 72, and 73 in excellent purities and yields. The authors suggest that this methodology could be utilized for the preparation of oligosaccharide libraries. 

Ether-linked oligosaccharides have been prepared from 5,6-anhydro-D-glucose derivatives,345 and 5,6-anhydro sugars have also afforded various polysaccharides.338,346... 

T. B. Grindley, G. J. Reimer, J. Kralovec, R. G. Brown, and M. Anderson, Syntheses of 3-deoxy-3-substituted-D-glucose derivatives. 1. Improvements in preparation of and nucleophilic additions to l,6 2,3-dianhydro-4-0-benzyi-/S-D-allopyranose, Can. J. Chem., 65 (1987) 1065-1071. 

Besides the D-glucose derivative just described, three other crystalline dichlorides have been prepared from 2-hydroxyglycals, namely, the dichlorides from 2,3,4,6-tetra-0-benzoyl-(2-hydroxy-D-glucal)10 (yield, 22%), 2,3,6,2, 3, 4, 6,-hepta-0-acetyl-(2-hydroxycellobial)IS (yield, 30%), and 2,3,4-tri-0-benzoyl-(2-hydroxy-D-xylal)12 (yield, 17%). The 2,3,4,6-tetra-0-benzoyl-l,2-dichloro-l-deoxy-D-hexose prepared from the first of these by short chlorination in benzene reacted with sodium acetate in hot, glacial acetic acid. The crystalline product was assigned the structure of l-0-acetyl-3,4,6-tri-0-benzoyl-D-glucosone10 since it is not converted to kojic acid by pyridine-acetic anhydride (see below). A benzoyl group has been lost. 

Acetamido-2-deoxy-D-glucose derivatives generally crystallize as the a anomer and mutarotate in polar solvents to a mixture of the two anomers, but the pure /3 anomer may be prepared by acylation of 2-amino-2-deoxy-(3-n-glucose at a low temperature with the acid anhydrides in A, A-dimeth-ylformamide solution.100 Mutarotation in this solvent is very slow, and the reaction product may be removed long before mutarotational equilibrium has been established. 

To be presented in the sequel, are a series of prototype reaction channels leading from simple, tautomerically fixed D-glucose derivatives to enantiopure building blocks along preparatively useful, practical protocols, followed by their utilization for the straightforward total synthesis of a series of natural and nonnatural products in optically active, enantiomerically homogeneous form. 

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