Recent advances in glycosylation reactions

Secondary amides react smoothly with benzylated glycosyl chlorides in the presence of a silver salt to give a new class of imidates which can be used in a novel method of a-glycoside synthesis.A practical and stereospecific approach to a variety of a-0-glucosides, a-0-galactosides, and a-L-fucosides is thereby provided.Applications of the method in the synthesis of several human blood group antigenic determinants is described together with other synthetic uses of sugar imidates. INTROOUCTIONMuch effort has been devoted (Ref. 1) in the last decade to the development of efficient and stereocontrolled syntheses of glycosides with the substituents at positions 1 and 2 in cisor trans-relationship (1 ,2-cis and 1 ,2-trans-glycosides).The subject is of paramount importance lnrelation to the synthesis of biologically and clinically active substances such as carbohydrate antigens and oligosaccharide-containing antibiotics.Although there is now a variety of methods for the selective activation of the anomeric centre of carbohydrates, the long-established reaction using a glycosyl chloride or bromideremeins one of the few methods of choice.This type of activation has been investigated widely since its introduction by Koenigs and Knorr (Ref.2) and has recently been developed to provide important procedures for the synthesis of 1,2-cis-disaccharides (Refs.1c, 3).The halide ion-catalyzed glycosylation reaction has been successfully applied by Lemieux ~t ~1.(Refs. 1 c, 4) to the synthesis of several blood group antigenic determinants.Recent results obtained in the author's Iaboretory in this field are now summarised. OISCUSSIONAlthough the alkylation of amides in the presence of silver salts to provide imidates isaweil established process, no application to halogene sugars has been reported so far.When a benzene solution of 2,3,4,6tetra-0-acetyl-a-0-glucopyranosyl bromide (l) was stirred at room temperature in the presence of N-methyl- acetamide, silver oxide, di-isopropylethylamine, and a molecular sieve (4 Ä), the imidate .!,(m.p. 98°) was obtained (80%).The 5 :!H H coupling constant (0.5 Hz) for the two methyl groups in 2.. indicates the S,-configuration.This reaction'is generaland a family of imldates has been prepared. AcO~Aco AcOAc Br Ac O : e _ Ac AcO 0 Me c--AcO II N, Me i , MeNHCOMe , Ag 2 0, mol.sieveAs might be expected, condensation of these acetylated imidates with alcohols in the presence of acid gave mainly orthoesters.For example, 2, 3,4,6-tetra-0-acetyi-1-0-(N-phenylacetimidyl)-ß-0-galactopyranose GD was condensed at room temperature with 1 ,2:3,4-di-0-isopropylidene-a-0-galactopyranose (4.) in benzene and in the presence of toluene-p-sulphonic acid to provide the orthoester 2•