Sugar synthesis cycloaddition reactions

Two approaches, based on furan, have found wide application in carbohydrate synthesis. Cycloaddition reactions of furan with 2-substituted acrylonitrile or acrolein lead to oxabicycloheptanes which, in tnm, can be transformed to monosaccharides. On the other hand, furfuryl alcohols can be converted—either by the Clauson-Kaas reaction or by mild oxidation—into 5,6-dihydro-4-pyrones, suitable for easy functionalization to sugars. 

A substantial amount of research has been carried out in the field of tetrazole-fused sugars (rhamnose, mannose, and glucose derivatives) - mostly because of the biological importance of these derivatives. In many of these cases synthesis of the fused tetrazole moieties has been perfected by intramolecular 1,3-cycloaddition reactions with participation of a cyano and azido group. Some of these results are shown in Schemes 26 and 27. 

An attractive entry to the carbohydrate synthesis is provided by the cycloaddition reaction. Hetero-Diels-Alder reaction, either between an oxa-diene (a,[3-unsaturated aldehyde) and an nucleophilic dienophile, or between activated diene and carbonyl compound (usually an aldehyde), leads to dihydropyrans, which can be subsequently functionalized to sugars in the desired manner (Scheme 3). 

Scheme 26 Synthesis of sugar-based monocyclic [S-lactams by Staudinger [2+2] cycloaddition reaction...

Intramolecular cycloaddition of fV-benzyl-substituted 3-O-allylhexose nitrones furnishes chiral oxepane derivatives. The regioselectivity of the cycloaddition depends on several factors such as (1) the structural nature of the nitrone, (2) substitution and stereochemistry at 3-C of the carbohydrate backbone, and (3) substitution at the terminus of the O-allyl moiety. A mixture of an oxepane and a pyran is formed in the intramolecular oxime olefin cycloaddition of a 3-O-allyl carbohydrate-derived oxime <2003T4623>. The highly stereoselective synthesis of oxepanes proceeds by intramolecular nitrone cycloaddition reactions on sugar-derived methallyl ethers <2003TA3899>. 

Several fully saturated heterocyclic systems which have been formed by cycloaddition reactions have found use in natural product synthesis. Cycloadducts (27) and (28) were prepared as part of an investigation into the synthesis of the benzoxocin fragment of the antitumor anthracycline nogalomycin <9lJOCl364> and cycloadducts (245) and (248) were intermediates in the synthesis of amino sugar derivatives <84JA5598>. 

---