Cycloaddition for the synthesis of disaccharides

Disaccharides, are active intermediates in many biological processes. Traditionally, these compounds are synthesized through the reaction of a carbohydrate precursor (glycosyl donor) and an incoming nucleophile (glycosyl acceptor) to provide a di- or oligo-saccharide. Both donors and acceptors are generally highly sensitive to the reaction conditions. For this reason, the development of optimal conditions for a particular donor and acceptor is often necessary.; Any method that can accomplish these syntheses under mild conditions will be well-received. This goal has been achieved in this project. We have developed the synthesis of disaccharides under practically neutral conditions.; The synthesis starts with the generation of a cycloadduct precursor of a disaccharide. Cycloadducts are obtained through the reaction of a chiral thiono-ketohexanolide with glycals, of the allo, gluco, and galacto series. The chiral ketohexanohde was successfully obtained through enzymatic yeast reduction of the acetoacetylated Meldrum's acid. We obtained top face addition with the tribenzyl allal, and below face addition with the gluco and galacto glycals in high stereoselectivity and in reasonable isolated yield.; The C-S bond cleavage was the final stage in our cycloaddition and we developed the conditions for this desulfurization using W-2 Raney nickel. Under this desulfurization procedure over-reduction and glycal elimination are avoided.; The cycloaddition between the chiral thiono-ketohexanolide and the 2-acetoxy tribenzyl glucal was also performed. Three regioisomers, were isolated and fully characterized. These regioisomers me precursors of parasorboside, and two more steps, desulfurization and deprotection, could produce this natural product.