Chemical synthesis of linear and cyclic unnatural oligosaccharides by iterative glycosidation of ketoses

The development of an efficient method for the stereoselective synthesis of alpha -D-(2 --> 1)-linked ketoside oligomers is described. The method is b ased on an iterative protocol composed of two key steps: a) the coupling of a thiazolylketosyl phosphite donor with an hydroxymethylketoside acceptor; and b) the introduction of the hydroxymethyl group at the anomeric carbon atom of the resulting oligomer, To high light its efficiency, the protocol was used in the assembly of D-galacto-2-heptulopyranose-containing oligoket osides through alpha-(2--> 1) linkages up to pentameric stage. The yield of the isolated oligomers ranged from 48% in the first cycle to 29% in the fo urth cycle. Having employed a pontenyl-substituted hydroxymethylketoside ac ceptor in the first cycle, all the derived oligomers contained the pentenyl group at their reducing end. This group was exploited to transform the lin ear oligomers into cyclic products through intramolecular glycosidation. Th r: major product derived from the linear trisaccharide was confirmed by X-r ay crystallography to be the cyclotris-(2 --> 1)-(alpha -D-galacto-2-heptul opyranosyl). The structure of this compound was essentially that of a [9]cr own-3 ether bearing three galactopyranose rings spiroanellated in a propell erlike fashion. This arrangement of carbohydrate units linked to the crown ether created a densely alkoxylated cavity suitable for the encapsulation o f alkali-metal cations (Li, Na, K, Ca, Mg).