Sugar-derived chirons

Isoxazoles and isoxazolidines fused with sugar systems are found to show biological activity. In a continuation of our studies on the utilization of a variety of protocols on the sugar-derived chirons we embarked onto the 1,3-dipolar cycloaddition reactions. Accordingly, intramolecular oxime olefin cyclo-addition (lOOC) reactions on the chiron (91 X=NOH) gave an isoxazolidine-fused saccharide (92) (Scheme 22.21). 

The naked sugars of the first generation (319, 320, 321, (+)-322, (—)-322) are useful chirons for preparing all kinds of rare sugars derivatives [180] and analogs such as C-linked disaccharides [181]. They have been converted into conduritols, cyclitols and carbahexose derivatives [174,182]. The bicyclic ketones can also be converted into their enoxysilanes and then cleaved by ozonolysis. Depending on the workup conditions, 2,5-anhydrohexaldaric acid or 2,5-anhydrohexonic acid derivatives can be readily prepared in both enantiomerically pure forms [183]. 

Other class of polyhydroxylated derivatives acting as sugar mimics consists of carbasugars i.e. sugars in which the ring-oxygen atom is replaced by the carbon atom. Their synthesis can be initiated either from achiral (or racemic) derivatives (this approach will not be dealt with) or more conveniently from simple sugars (chirons). Syntheses of these important compounds were comprehensively reviewed recently.4... 

S. Jeganaihan and P. Vogel, Highly stereoselective total syntheses of octoses and derivatives, J. Org. Chem. 56 1133 (1991) P. Vogel, D. Fattori.F. Gasparini, and C. Le Drian, Optically pure 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives ( naked sugars ) as new chirons, Synlett. p. 173 (1990). 

Enantiomerically pure 7-oxanorbornenyl derivatives 319, 320, 321, their saponification products (recovery of the chiral auxiliary in the aqueous phase) and ketones (+)-322 and (—)-322 are coined naked sugars of the first generation because they are chirons (= enantiomerically pure synthetic intermediates) like those derived from natural hexoses. Like natural sugars, they are enantiomerically pure. However, unlike natural sugars, they possess three unsubstituted (naked) carbon centers, the substitution of which follows highly stereoselective methods giving polysubstituted 7-oxabicyclo[2.2.1]heptane-2-ones that can be oxidized into the corresponding uronolactones as illustrated below. 

Vogel has developed 7-oxanorborn-5-en-2-one 2 and its derivatives as versatile alternative synthons for sugar chirons hence these substrates have been coined naked sugars. Several reviews summarizing this work have appeared [11]. The key cycloaddition in the synthesis is a Diels-Alder reaction between... 

For the stereoselective synthesis of C-glycosides, deoxygenation of hemiketals, obtained from Wacker oxidation of sngar-derived olefin alcohols, was envisaged as an easy and efficient protocol. In our earlier study on the synthesis of 4-epiethisolide, attempted PdCV mediated conversion of the terminal olefin (1), obtained from sugar chiron into a methyl ketone (2) resulted in the exclnsive formation of an anti-Markovnikov product (3), which happened to be the first report in the literature (Scheme 22.1). 

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