Serine and Threonine Schiff Base Esters React with β-Anomeric Peracetates in the Presence of BF3·Et2O to Produce β-Glycosides

Abstract

Improved procedures are reported for the glycosylation of L-serine and L-threonine utilizing activated Schiff base glycosyl acceptors, which are less expensive and more efficient alternatives to published methods. L-serine or L-threonine benzyl ester hydrochloride salts were reacted with the diarylketimine bis-(4-methoxyphenyl)-methanimine in CH3CN at rt to form the more nucleophilic Schiff bases 3a and 3b in excellent yield. These Schiff bases exhibited ring-chain tautomerism in CDCl3 as shown by 1H NMR. Schiff bases 3a and 3b, acting as glycosyl acceptors, reacted at rt with simple sugar peracetate donors with BF3·OEt2 promotion to provide the corresponding L-serine and L-threonine O-linked glycosides in excellent yields and purities. The dipeptide ester Schiff base Ar2C = N-Ser-Val-OCH3 3e also reacted to provide β-glycosides in excellent yields, and without epimerization. With microwave irradiation the reactions were complete in 2 to 5 min. To investigate this reaction further, classical AgOTf-promoted Koenigs-Knorr reaction of D-glucopyranosyl, lactosyl, and maltosyl bromides were examined, providing the β-glycosides with yields ranging from 35% to 68%. The difference in reactivity between α- and β-carbohydrate peracetate donors was remarkable. The less configurationally stable D-xylopyranosyl tetra-acetate (a pentose) showed no selectivity (αvsβ-configuration) toward the Schiff bases.