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

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 alpha -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 do nors 3-8, together with parameters influencing the stereochemistry of glyco sylation, such as protecting groups, catalysts, and dielectric constants of solvents. Although high alpha -selectivities have often been reported for fucosylation reactions with glycosyl accepters, complete alpha -selectivity was never observed here, using linear spacer alcohols 9-16. Generally, the best alpha -selectivities were obtained in fucosylations of the alcohols u nder in situ anomerization conditions using tetrabutylammonium bromide (75- 90% alpha -anomer), whereas promotion by NIS/TfOH(cat.) proceeded with poor stereoselectivity in treatment of the ethyl thiofucosides 3-5. No directin g effects from the 4-O protecting groups were noted. For the 2-O-benzyl-pro tected 1-O-thioethyl fucopyranosyl donors 3-5, electronic effects of the fu cosyl donor could not explain the observed stereoselectivity. The differenc e between the observed selectivities for alpha -fucosylations of glycosyl a ccepters, in comparison with the linear spacer alcohols used here, is proba bly due to steric effects of the more bulky glycosyl accepters.