ChemInform Abstract: De novo Synthesis of Carbohydrates and Related Natural Products

Abstract

Two synthetic strategies from achiral precutsors especially useful for sugars requiring unusual functional groups, deoxy and branched sugars, as well as partially 0protected sugars, are outlined. One strategy employs inversetype hetero-Diels-Alder reaction with highly functionalized 1-oxa-1,3-dienes. Their reaction with electron rich heterodienophiles (enol ethers, etc.) and subsequent diastereoselective transformation of the CC-double bond in the dihydropyran adducts obtained gives convenient access to deoxy sugars (for instance, Dand L-olivose) and related compounds, which also contain C-branching (for instance, ramulosin). The other versatile strategy starts from racemic or meso-divinyl glycols. Kinetic resolution via Sharpless epoxidation again gives direct access to partially 0protected carbohydrates. This method is exemplified in deoxy sugar synthesis (for instance, Dand L-digitoxose and chalcose) and also in the synthesis of the pheromone exobrevicomin. INTRODUCTION AND STRATEGIES Carbohydrate derivatives and related natural products are mainly synthesized by transformation of readily available sugars (ref. 1). However, the high density of functional groups of comparable reactivity requires regioselective protection and deprotection measures and stereospecific functional group exchange quite often resulting in multistep syntheses. Several methods have been developed in the last years which are useful in the diastereoselective and enantioselective generation of new stereocenters (ref. 2). Therefore novo syntheses or total syntheses of natural products from achiral starting materials have become competitive or even superior (ref. 3-8). For the generation of several subsequent chiral centers two different key step reactions are applicable: (i) stereoselective CC-bond formation and (ii) stereoselective functionalisation of compounds having already the required carbon skeleton. In the de novo synthesis of carbohydrates these two principles, •having led to great progress in natural product synthesis, are especially well illustrated (ref. 5-7). The stereoselective formation of the carbon skeleton is frequently attained by diastereofacial selectivity in carbon nucleophile additions to carbonyl and imine systems where either the nucleophile or the electrophile or both contain chiral groups in order to induce the preferred formation of one enantiomer (ref. 9, 10). Also Diels-Alder reaction has become a powerful tool in natural product synthesis because it combines CC-bond formation with diastereoselectivity at several centers (ref. 11). Due to supra-suprafacial reaction, polarity controlled orientation, and endoor exo-selectivity of diene and dienophile, very often only one pair of enantiomers is obtained out of the maximum of thirty two possible isomers (ref. 7). Recently even enantioselectivity could be incorporated successfully into the Diels-Alder reaction leading to preferential or exclusive formation of one single isomer (ref. 12). Aiming at the pyranose form of sugars hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems which are important targets in the chiron approach * De novo Synthesis of Carbohydrates and Related Natural Products, Part 25. Part 24, see ref. 23.