Carbohydrate derivatives, nitrile oxide

The chiral induction of carbohydrate enol ethers in 1,3-DC with some aromatic nitrile oxides was investigated. The highest diastereoseletivity (28 1 dr) was achieved with a 3-0-vinyl-p-D-fructopyranose derivative and 2,4,6-trimethylbenzonitrile oxide <02TA2535>. 

Chiral dipolarophiles such as 43 <03TL1071> and 45 <03SL1358>, derived from carbohydrates, react with nitrile oxides to afford spiro- and bicyclic-isoxazolines 44 and 46, respectively, with high regio- and diastereoselectivity. 

Most of the efforts toward stereocontrolled syntheses of 2-isoxazolines have been based on reactions between chiral dipolarophiles and achiral dipoles. This approach is exemplified by some selected examples in Schemes 112-114 and Equation (80). Enantiopure dipolarophiles such as 485 <2003TL1071> and 487 <2003SL1358>, derived from carbohydrates, reacted with nitrile oxides to afford spiro- and bicyclic-isoxazolines 486 and 488, respectively, with high regio- and diastereoselectivity (Scheme 112). 

A comprehensive review (260 refs.) on the synthesis of carbohydrates from noncarbohydrate sources covers the use of benzene-derived diols and products of Sharpless asymmetric oxidation as starting materials, Dodoni s thiazole and Vogel s naked sugar approaches, as well as the application of enzyme-catalysed aldol condensations. The preparation of monosaccharides by enzyme-catalysed aldol condensations is also discussed in a review on recent advances in the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics, in parts of reviews on the formation of carbon-carbon bonds by enzymic asymmetric synthesis and on carbohydrate-mediated biochemical recognition processes as potential targets for drug development, as well as in connection with the introduction of three Aldol Reaction Kits that provide dihydroxyacetone phosphate-dependent aldolases (27 refs.). A further review deals with the synthesis of carbohydrates by application of the nitrile oxide 1,3-dipolar cycloaddition (13 refs.). ... 

Further attempts to increase the kinetics and biocompatibility of 1,3-dipolar cycloadditions led organic chemists to explore altemative dipoles that react with multiple-bond reaction partners. Nitrile oxides are highly reactive dipoles that can react with various alkenes and alkynes to provide isoxazolines and isoxazoles, respectively. In the absence of a suitable reacting partner, nitrile oxides tend to dimerize to form fiiroxane derivatives, or can alternatively act as electrophiles. However, when generated in situ from suitable precursors such as hydroximoyl chlorides or by mild oxidation directly from oximes, nitrile oxides were successfully applied to the labeling of nucleic acids [43], peptides [44] and carbohydrates [45] (Fig. 7). 

This chapter, therefore, ends the monograph with a potpourri of reactions all of which occur without a change in oxidation state. In many cases, the reaction is one of nucleophilic attack at an electrophilic C-atom. The result is often hydrolytic bond cleavage (e.g., in carbohydrate conjugates, disubstitut-ed methylene and methine groups, imines, oximes, isocyanates, and nitriles, and various ring systems) or a nucleophilic substitution (e.g., hydrolytic de-halogenation of halocarbons and chloroplatin derivatives, and cyclization reactions). The formation of multiple bonds by dehydration is a special case to be discussed separately. 

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