Orthoesters glycosylation methods

P. J. Garegg and I. Kvamstrom, The orthoester glycosylation method. Variations in the anomeric composition of the product with aglycone basicity in the two step procedure, Acta Chem. Scand. B, 30 (1976) 655-658. 

Orthoesters were encountered in the methanolysis of tetra-0-(p-nitro-benzoyl)-j3-D-fructopyranosyl bromide while the main product (60%) was the result of direct inversion (a-pyranoside), the /3-anomer and the bicyclic compounds (22) and (23) were all formed to the extent of about 12%. The orthoester glycosylation method has been used to obtain a j3-D-glucopyranosyl porphyrin derivative and 3-D-ribopyranosides of strophanthidin and digitoxi-genin. 

Orthoester to Glycoside Rearrangement - The Two-Stage Glycosylation Method Revisited... 

From a historic perspective glycosyl chlorides and bromides introduced, respectively, by Michael [2] and Koenigs and Knorr [3] were the most widely used donors in the saccharide synthesis for a very long time. The introduction of 1,2-orthoesters in 1964 [4] was the first important attempt to find an alternative to the Koenigs-Knorr method. However, Paulsen in his 1990 review of reliable donors for glycosyl... 

The synthetic potential of the CMGL synthons is not limited to their ability to be easily opened in the presence of nucleophilic species. Indeed, subsequent functionalisation at position 2 provides 1,2-bisfunctionalised carbohydrates in an easy, general and competitive manner (Scheme 18).3e This offers an alternative to other methods, notably glycosylation reactions81 using intermediates such as 1,2-isopropylidene acetals,82 1,2-orthoesters,83... 

This method works very well for reactive glycosyl acceptors such as primary alcohols. It can be carried out without affecting other acid sensitive functionalities including acetonides and even orthoesters. Nishimura and co-workers successfully employed this method to prepare the ttisaccharide monomer 344 (Scheme 8.107). After deprotection, the product was copolymerized with acrylamide to give a biologically interesting glycoprotein model. 

Kochetkov NK, Bochkov AF, Sokolavskaya TA, Snyatkova VJ. Modifications of the orthoester method of glycosylation. Carb. Res. 1971 16 17-27. 

Trichloroacetimidates function well as donors also with saccharide thiol acceptors. A number of thiodisaccharides have accordingly been prepared using this method [169,170,171,172,173], Possible by-products are various elimination products and orthoester formation. The stereochemical outcome is not easy to predict or control and, as so often in carbohydrate chemistry, an optimization of conditions is usually necessary for each glycosylation. For example, the use of an acetylated o -trichloroacetimidate glucose donor can yield not only an almost exclusively -linked disaccharide product but also preferentially an a-linked product, depending on the acceptor and conditions used ( Scheme 53) (see also Sect. 3.3). 

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