Carbohydrates, cyclizations

C. S. Wilcox and L. M. Thomasco, New syntheses of carbocycles from carbohydrates. Cyclization of radicals derived from unsaturated halo sugars, J. Org. Chem. 50 546 (1985) see also S. Hanessian, D. S. Dhanoa, and P. L. Beaulieu, Synthesis of u>-substitoted a,p-unsaturated esters via radical-induced cyclizations. Can. J. Chem. 65 1859 (1987). 

Wilcox CS, Tomasco LM (1985) New syntheses of carbocycles from carbohydrates. Cyclization of radicals derived from unsaturated halo sugars. J Org Chem 50 546-547... 

Since 1,5-dienes can be cyclized by palladium salts via cr,7r-complexes [36], it appears probable that similar intermediates are involved in the carbohydrate cyclizations. 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

In another version of this method, the radical generated by radical exchange from the aryl telluride carbohydrate 83 and the N-acetoxy-2-thiopyridone affords, after intramolecular cyclization and desulfanylation, the polyhydroxylated and phosphorylated pseudo sugar 84 [54] (Scheme 23). 

Recent applications of HPAEC-PAD are many and varied. A representative list includes quantitation of polyglucose metabolites in plasma of dialysis patients,148 analysis of heat-treated milk,149 carbohydrate content in lipopolysaccharides,150 phosphorylated sugars in tissue samples,151 composition of soybean meal,152 carbohydrate composition of recombinant modified tissue plasminogen activator,153 analysis of cyclization products from an enzyme reaction,154 carbohydrate content of glycoconjugate vaccines,155 and monitoring of patients with rheumatoid arthritis.156... 

Moreover, the reaction with Y = OCH3 and the stereochemical control of analogous hex-5-enyl radical cyclizations has also been studied. This method constitutes part of a synthetic route from carbohydrates to optically active carbocycles.[74],[75]... 

A useful and simple method for the one-pot preparation of highly functionalized, enanhomerically pure cyclopentanes from readily accessible carbohydrate precursors has been designed by Chiara and coworkers [73]. The procedure depends on a samarium(II) iodide-promoted reductive dealkoxyhalogenahon of 6-desoxy-6-iodo-hexopyranosides such as 7-160 to produce a 6,e-unsaturated aldehyde which, after reductive cyclization, is trapped by an added electrophile to furnish the final product. In the presence of acetic anhydride, the four products 7-161 to 7-164 were obtained from 7-160. 

This section presents selected examples of the use of zeolites and related porous materials for transformations of carbohydrates, that fall beyond the scope of the previous paragraphs. They include the use of zeolites in click chemistry and in a variety of reactions, including the synthesis of anhydro sugars, cyclization, elimination, and addition reactions to the carbonyl group. 

The observation of a stereoconvergent cyclization by Roy et al. [18], as shown in the third example, is of special interest from a synthetic point of view because it exploits the configurational lability of radicals in a favorable manner. The other examples, i. e. Nugent and RajanBabu s cyclization of a carbohydrate-derived epoxide [5d] and Clive s quinane synthesis [19], amply demonstrate the usefulness of the titanocene-initiated epoxide opening. 

In carbohydrate chemistry, the most described method for the preparation of saccharidic thionocarbamates involves preliminary introduction of the amine function on a partially or non-protected saccharidic template. The condensation of amino sugars with carbon disulfide or thiophosgene leads to cyclization in 1,3-oxazolidine- or l,3-oxazine-2-thiones. This reaction involves the formation of an intermediate isothiocyanate, which reacts further with a 3- or y-located hydroxyl group. The viability and facility of this process depends on the saccharidic ring size and the inherent strain. Some major rules can be put into light from the cases studied 30... 

Saccharidic templates bearing an amino group in C-2, C-6, C-3, C-5. Generally, an amine located on non-anomeric position reacts similarly through the condensation reaction with carbon disulfide or thiophosgene, the preliminary formed isothiocyanate leads to spontaneous or base-induced cyclization into 1,3-oxazolidine- or l,3-oxazine-2-thiones, as previously mentioned. Several extensive studies are reported about the selective introduction of thionocarbamate moieties on carbohydrate scaffolds.3 22 23 320 34 38... 

A carbohydrate based approach to the synthesis of polyketide acid unit present in nagahamide A has been reported. Reductive transformation of 183 followed by cyclization allowed to prepare 184 (Fig. 58).75... 

In a more complex elaboration of the hydrogen atom abstraction/nucleo-philic cyclization route to tetrahydrofurans (Scheme 20), a carbohydrate-based N-alkoxy phthalimide was converted to a spirocyclic acetal in excellent yield and diastereoselectivity (Scheme 33) [136]. In this cyclization, nucleophilic attack takes place from the endo face of the trioxabicyclo [3.3.0] octane... 

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. 

Unsaturated carboxylic acids can be de-carboxylated to alkyl radicals that undergo an intramolecular addition. The S-exo-trig-cyclization of fi-allyloxy radicals, generated from an appropriate carboxylic acid, combined with a final heterocoupling has been applied to synthesize a precursor of prostaglandine PGF2q (Fig. 47) [246] and a branched carbohydrate (ratio of diastereo-mers 1.8 1) (Fig. 48) [247]. A radical tandem cyclization of a doubly unsaturated monocyclic carbocyclic acid provides a... 

S. Castro and M. W. Peczuh, Sequential cyclization-elimination route to carbohydrate-based oxepines, J. Org. Chem., 70 (2005) 3312-3315. 

W. S. Fyvie, M. Morton, and M. W. Peczuh, Synthesis of 2-iodo-2-deoxy septanosides from a D-xylose-based oxepine Intramolecular cyclization in the absence of a glycosyl acceptor, Carbohydr. Res., 339 (2004) 2363-2370. 

With respect to five-membered lactones fused to hexopyranose units, some approaches have been reported so far and the exploitation of their synthetic potential has led to the access of new carbohydrate derivatives. Bicyclic derivatives of this type are key intermediates in the synthesis of the epimer at C-3 of the sugar moiety contained in miharamycins [212, 213]. The latter are antibiotics known to inhibit strongly Pyricularia oryzae, which produces the rice blast disease. These compounds are also considered to be a potential bioterrorism agent (Scheme 42). Hence, the 3,3-spiroepoxide 176 was converted into the 3-C-cyanomethyl derivative 177, the hydrolysis of which led to spontaneous cyclization in the presence of... 

Activation of the hydroxyl group as an acetate leaving group to promote oxazoline formation has been applied extensively in carbohydrates to afford p-glycosylation with high selectivity. A Lewis acid such as ferric chloride (FeCL), tin chloride (SnCLt), or TMSOTf is usually added to facilitate cyclization. Several recent examples are shown in Scheme 8.20. Compound 54 has been further elaborated to 1,2-dideoxynojmmycin 54a, a potent p-Al-acetylglycosamine inhibitor. 

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