Open-chain carbohydrate derivatives

Open-chain carbohydrate derivatives are ideal objects for conformational analysis by H -NMR solution spectroscopy. The OH-proton signals are well separated from CH-methine proton signals, and decoupling experiments allow easy signal assignments. Polar carbohydrate derivatives and the carbohydrates themselves are soluble in dimethyl sulfoxide (DMSO), which destroys all inter-... 

Figure 4.2.6 Two effects determine the configurations of open-chain carbohydrate derivatives (a) gauche confirmations are favored in 1,2-diols over anti conformations, and (b) 1,3-syn diaxial interactions between hydroxyl substituents are repulsive and often lead to distortions of the all-anti chain.

Cyclization by Displacement of Leaving Groups in Carbohydrate Substrates by Amines. The synthesis of l,2,4-trideoxy-l,4-imino-D-erythro-pentitol (31) has been achieved in eight steps, in 42% overall yield, from 2,5-di-O-p-tol-uenesulfonyl-D-ribono-1,4-lactone according to Scheme 7. The correct stereochemistry in the product was achieved by epimerization at C-4 in a 5-0-tosylated 2-deoxy lactone intermediate base action on the lactone produced a 4,5-epoxide of an open-chain carboxylate derivative which subsequently ring-closed by intramolecular attack of the carboxylate anion on the epoxide to produce the diastereomeric lactone. ... 

Participation by the acetal function is common in displacement reactions of carbohydrate derivatives. An example of participation by an acetal group in an open-chain carbohydrate has been provided by Hughes and Speakman. Treatment of ribose derivative (152) with tetrabutyl-ammonium benzoate in 1-methylpyrrolidone gave 2,3,5-tri-0-benzyl-4-0-methyl-L-lyxose methyl hemiacetal 1-benzoate (154) instead of the expected 4-O-benzoyl-L-lyxose derivative. The oxonium ion (153) was thought to be an intermediate. 

If the carbonyl and the hydroxyl group are in the same molecule, an intramolecular nucleophilic addition can take place, leading to the formation of a cyclic hemiacetal. Five- and six-membered cyclic hemiacetals are relatively strain-free and particularly stable, and many carbohydrates therefore exist in an equilibrium between open-chain and cyclic forms. Glucose, for instance, exists in aqueous solution primarily in the six-membered, pyranose form resulting from intramolecular nucleophilic addition of the -OH group at C5 to the Cl carbonyl group (Figure 25.4). The name pyranose is derived from pyran, the name of the unsaturated six-membered cyclic ether. 

The reaction of carbohydrate-derived imines with the Danishefsky diene, ( )-1 -methoxy-3-(trimethylsilyloxy)butadiene, to form heterocycles via the open-chain adducts (for assignment, see pp 456 and 478)130. 

Addition of allyl species to the free sugar 106 affords an open-chain unsaturated carbohydrate 107. In a few well-defined steps the furyl derivative 108 is obtained, which upon oxidation with peroxide provides finally the higher carbon sugar 109 (O Scheme 47). 

The cyclic carbohydrate derivative 1 reacts with the 2-quinone methide obtained from the benzocyclobutene 2 to give cycloadducts 3-6 with a 92% overall yield. The regioselectivity (3-6 vs. 7) is 9 1 with a diastereoselectivity d.r. [(3S)/(3/ )] 83 17 within the series of correct regioselectivity. Adducts 3 and 4 can be converted into the open-chain product 5 and further transformed to give the aureolic acid precursor 827. 

Other carbohydrate-derived dienes in the open-chain form have also been investigated. Dienes 5, upon addition to the quinone 6, generated in situ from hydroquinone, reportedly give single adducts 7, which are epimerized on basic alumina to compounds 82. 

Synthesis from o-glucose Various methods have been reported for the synthesis of trehazolamine (3) from carbohydrate precnrsors such as D-glucose. Thus, the 4,6-benzylidene derivative 10, easily prepared from D-glucose, was converted quantitatively to the respective open chain 0-methyloxime derivative (Scheme 2) Subsequent oxidation ... 

The keto-enol and thione-thiol tautomerisms in pyridine and pyrimidine derivatives were already discussed in Chapter 6. Azo-hydrazo tautomerisril, CH—N=N C=N—NH, has been studied by Burawoy and co-workers34. Another type of tautomerism has been identified in the case of carbohydrates. The proportions of the ring and open structures of carbohydrates have been determined by measuring the intensity of the 280 mp carbonyl band. Pacsu and Hiller have shown that D-glucose exists almost completely in the ring form in neutral solution and to the extent of 0T per cent in the open chain form in acid solution. 

In the fourth approach, the carbohydrate can be reversibly converted into a glycosylamine by treatment with an ammonium salt (263,264) or an aliphatic amine (265,266). However, these derivatives are quite unstable in slightly acidic medium or neutral medium. They are further stabilized by acylation with, for example, anhydride acetic (265), p-vinylbenzoyl chloride (267), acryloyl chloride (263), or chloroacetic anhydride, followed by ammonolysis (268) (Fig. 36). The N-linked structure of these glycosynthons is distinct from the open chain structure of the carbohydrate derivatives described above. This method may be useful to introduce complex oligosaccharides. 

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