Fucosylation of linear alcohols : A study of parameters influencing the stereochemistry of glycosylation

Abstract

L-Fucose is a constituent of many glycoconjugates and often has a key role in the epitope involved in biological functions. The chemical synthesis of such compounds is necessary to generate sufficient material to explore the molecular details of their bioactivity. In this context, the development of practical and stereoselective α-fucosylation reactions is essential. Here are described several procedures for fucosylation of linear alcohols 9-16 with L-fucose (1) and a series of 2-O-benzyl-protected fucopyranosyl donors 3-8, together with parameters influencing the stereochemistry of glycosylation, such as protecting groups, catalysts, and dielectric constants of solvents. Although high α-selectivities have often been reported for fucosylation reactions with glycosyl acceptors, complete α-selectivity was never observed here, using linear spacer alcohols 9-16. Generally, the best α-selectivities were obtained in fucosylations of the alcohols under in situ anomerization conditions using tetrabutylammonium bromide (75-90% α-anomer), whereas promotion by NIS/TfOH(cat.) proceeded with poor stereoselectivity in treatment of the ethyl thiofucosides 3-5. No directing effects from the 4-O protecting groups were noted. For the 2-O-benzyl-protected 1-O-thioethyl fucopyranosyl donors 3-5, electronic effects of the fucosyl donor could not explain the observed stereoselectivity. The difference between the observed selectivities for α-fucosylations of glycosyl acceptors, in comparison with the linear spacer alcohols used here, is probably due to steric effects of the more bulky glycosyl acceptors.