Nitrones sugars

Several approaches based on nitro-aldol for the synthesis of amino sugars have been reported Alumina-catalyzed reaction of methyl 3- nitropropanoate with O-benzyl-o-lactaldehyde gives the o-ribo-nitro-aldol fanti, and isomeri in 63% yield, which is converted into L-dannosamine fsee Secdon 3 3 Jager and coworkers have reported a short synthesis of L-acosamine based on the stereoselective nitro-aldol reaction of 2-O-benzyl-L-lactaldehyde with 3-nitropropanal dimethyl acetal as shovm in Scheme 3 10 The stereoselecdve nitro-aldol reacdon is carried ont by the silyl nitronate approach as discussed in Secdon 3 3... 

Fisera L (2007) 1,3-Dipolar Cycloadditions of Sugar-Derived Nitrones and their Utilization in Synthesis. 7 287-323... 

Oxidation with Mn02 of N-glycosylhydroxylamines (48), obtained in the reaction of sugars (47), with A -methyl- and N -benzylhydroxylamines, leads selectively to the corresponding C -unsubstituted and C-phenyl-iV-glycosyl nitrones (49) (Scheme 2.18) (118, 119). 

Another synthetic approach for generating sugar-containing nitrones is by initial treatment of sugars with unsubstituted hydroxylamine. The resulting cyclic hydroxylamine of the tautomeric mixture (68a) and of the open chain oxime (68b) react with aldehydes to give the corresponding nitrones (69) (Scheme 2.24) (216-220). 

More recently, the synthesis of relatively stable chiral acyl nitronates by the reactions of acetic anhydride and pyridine with secondary nitro sugar derivatives has been documented (221). 

Recent research deals with stereoselective 1,3-dipolar cycloadditions of nitrones for the syntheses of alkaloids and aza heterocycles asymmetric synthesis of biologically active compounds such as glycosidase inhibitors, sugar mimetics, /3-lactams, and amino acids synthesis of peptido-mimetics and peptides chemistry of spirocyclopropane heterocycles synthesis of organic materials for molecular recognition and photochemical applications. 

Intramolecular nitroaldol reactions are a useful choice for the conversion of sugars into polyhydroxylated nitro cyclopentanes, nitro cyclohexanes and their derivatives.46 Baer et al. in the course of their studies on the cyclization of 6-deoxy-6-nitrohexoses under kinetic and thermodynamic control,47 established the reaction pathway involved in the formation of nitroinositols mediated by intramolecular Henry reactions. Firstly, a nitronate is formed and then, under thermodynamic control conditions, an epimerization occurs before cyclization. But, under kinetic controlled conditions, the cyclization occurs first.48... 

C-Alkylation has also been observed in intramolecular reactions where the O-alkylation is not favoured.76 This property has been recently exploited in a stereocontrolled intramolecular cyclization of nitronate of nitro sugar 101 (Scheme 32), that provided the novel bicyclic nitrolactone 102, a synthetic precursor of tripeptide 103, that includes the first reported polyhydroxylated cyclopentane (3-amino acid.77... 

The synthesis of these important compounds is very well explored. They can be now prepared almost routinely by a number of methods including the RCM cyclization of the properly activated sugar diolefins, 1,3-dipolar cycloaddition of nitrones and olefins (recent review ref. 6) or other types of cyclizations. 

The 1,3-dipolar cycloaddition. The interesting approach to aza-disaccharides in which the aza-part is linked to normal sugar was proposed by Martin.7 The sugar nitrone 1 reacted with 5-O-allyl-galactofuranoside to afford adduct 2 (Fig. 1). 

Synthesis of bicyclic aza sugars from D-xylose was reported. A key step involved reaction of the nitrone 9 with ethyl acrylate providing intermediate 10, which was finally converted into aza sugars (Fig. 4).11... 

The 1,3-dipolar cycloaddition of nitrone 12 (derived from D-glucose) was also used for the preparation of bicyclic aza sugars of type 14 (route a Fig. 5).12 Another classical approach (route b) allowed to prepare the analogs (e.g. 17).13,14... 

The 1,3-dipolar cycloaddition between the sugar nitrone and sugar olefins was proposed54 and an example is shown in Fig. 39.54e... 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

Borrachero et al. (180) prepared a number of sugar isoxazolidines by the reaction of carbohydrate-functionalized nitrones with nitroalkenes (Scheme 1.33). They found a matched pair of chiral sugar cycloaddition reaction partners to be... 

An impressive enantiopure synthesis of Amaryllidaceae alkaloids has been achieved through the formation of sugar-derived homochiral alkenyl nitrone 265 (Fig. 1.7).[280] While this reagent required lengthy preparation, it underwent an intramolecular dipolar cycloaddition to establish the required stereochemistry of the polycyclic pyrrolidine skeleton of (—)-haemanthidine (266), which was converted to (+)-pretazettine and (+)-tazettine by established procedures (281). 

The tandem transesterification/[3 + 2]-cycloaddition methodology is be a powerful synthetic tool, since it guarantees high diastereoselectivity even under thermal conditions. It has been successfully apphed to synthetic work of the N-terminal amino acid component of Nikkomycin Bz (Scheme 11.53) (173). Thus, the sugar-based oxime is condensed with a glyoxylate hemiacetal to produce a chiral nitrone ester, which is then reacted with ( )-p-niethoxycinnamyl alcohol in the presence of a catalytic amount of TiCU at 100 °C. After the intramolecular cycloaddition, the... 

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