The reaction of silylated nucleophiles with 6,1-anhydroglucopyranuronic acid (glucuronic acid 6,1-lactones) catalysed by tin(IV) chloride provides 1,2-trans or 1,2-cis (deoxy)glycosides in a manner dependent on the donor structure. The alpha-glycoside was obtained for reactions of the donor with the 2-acyl group and 2-deoxydonors, whereas the 2-deoxy-2-iodo donor gave the beta-glycoside. Experimental evidence shows that when 1,2-cis-glycoside formation occurs, the anomerisation of initially formed 1,2-trans-glycosides catalysed by SnCl(4) is possible. The anomerisation of beta-D-glucopyranosiduronic acids was found to be faster, in some cases, than anomerisation of related beta-D-glucopyranosiduronic acid esters and beta-D-glucopyranoside derivatives and the rates are dependent on the structure of the aglycon. Moreover, the rates of anomerisation of beta-D-glucopyranuronic acid derivatives can be qualitatively correlated with rates of hydrolysis of beta-D-glucopyranosiduronic acids. Mechanistic possibilities for the reactions are considered.

Stereoselective glycoside synthesis is of interest because of the biological and medical relevance of oligosaccharides, glycoproteins, glycolipids, [1] and other carbohydrate derivatives, [2] and a range of strategies have been developed to produce these compounds.[3] The 1,6-lactone derivative 2 (see Scheme 1) has potential for use in the synthesis of 1,2-cisglycosides [4] but its application has been limited because of the low yields obtained from its reaction with alcohols.[5] We now report that the SnCl 4 -catalyzed coupling of silyl ethers [6] with 2 provides a-O-glucuronides in significantly improved yields without loss of stereoselectivity. The methodology has been extended to the related 2-deoxylactones, which give aor b-glycosides depending on the structure of the donor.The preparation of 2 was carried out via the mixed anhydride 1 (Scheme 1) by an improved and shorter procedure than that previously described.[5] The donors 6 and 7 were also prepared, via glycal 4, because of their potential for the synthesis of 2-deoxyglycosides, which are of biological interest.[7] Thus, the reaction of the allyl ester 3 with hydrogen bromide in acetic acid gave a glycosyl bromide intermediate

The solution structure of glycosyl amides has been studied by using NMR. A strong preference is displayed by tertiary aromatic glycosyl amides for E-anti structures in contrast with secondary aromatic glycosyl amides where Z-anti structures predominate. The structural diversity displayed by these classes of molecules would seem to be important as the directional properties of the aromatic ring, or groups attached to the aromatic ring, would be determined by choosing to have either a secondary or tertiary amide at the anomeric center and could be considered when designing bioactive molecules with carbohydrate scaffolds. The structural analysis was also carried out for related divalent secondary and tertiary glycosyl amides and these compounds display preferences similar to that of the monovalent compounds. The constrained divalent compounds have potential for promoting formation of clusters that will have restricted structure and thus have potential for novel studies of mechanisms of action of multivalent ligands. Possible applications of such compounds would be as scaffolds for the design and synthesis of ligands that will facilitate protein-protein or other receptor-receptor interactions. The affinity of restricted divalent (or higher order) ligands, designed to bind to proteins that recognize carbohydrates which would facilitate clustering and concomitantly promote protein-protein interactions, may be significantly higher than monovalent counterparts or multivalent ligands without these properties. This may be useful as a new approach in the development of therapeutics based on carbohydrates.

No abstract

Stereoselective glycoside synthesis is of interest because of the biological and medical relevance of oligosaccharides, glycoproteins, glycolipids, [1] and other carbohydrate derivatives, [2] and a range of strategies have been developed to produce these compounds.[3] The 1,6-lactone derivative 2 (see Scheme 1) has potential for use in the synthesis of 1,2-cisglycosides [4] but its application has been limited because of the low yields obtained from its reaction with alcohols.[5] We now report that the SnCl 4 -catalyzed coupling of silyl ethers [6] with 2 provides a-O-glucuronides in significantly improved yields without loss of stereoselectivity. The methodology has been extended to the related 2-deoxylactones, which give aor b-glycosides depending on the structure of the donor.The preparation of 2 was carried out via the mixed anhydride 1 (Scheme 1) by an improved and shorter procedure than that previously described.[5] The donors 6 and 7 were also prepared, via glycal 4, because of their potential for the synthesis of 2-deoxyglycosides, which are of biological interest.[7] Thus, the reaction of the allyl ester 3 with hydrogen bromide in acetic acid gave a glycosyl bromide intermediate