DIFFERENTIAL REACTIVITY OF CARBOHYDRATE HYDROXYLS IN GLYCOSYLATIONS .2. THE LIKELY ROLE OF INTRAMOLECULAR HYDROGEN-BONDING ON GLYCOSYLATIONREACTIONS - GALACTOSYLATION OF NUCLEOSIDE 5-HYDROXYLS FOR THE SYNTHESES OF NOVEL POTENTIAL ANTICANCER AGENTS

Contrary to expectations, many primary hydroxy groups are completely u nreactive in glycosylation reactions, or give the desired glycosides i n very low yields accompanied by products of many side reactions. Hydr ogens of such primary hydroxyls are shown to be intramolecularly hydro gen bonded. Intermediates formed by nucleophilic attack by these hydro xyls on activated glycosylating agents may resist hydrogen abstraction . This resistance to proton loss is postulated to be the origin of the observed unreactivity. It is shown that successful glycosylations tak e place under acidic conditions under which such hydrogen bonds cease to exist. Accordingly, direct galactosylations of the normally unreact ive 5'-hydroxyls of nucleosides were accomplished for the first time w ith a galactose trichloroacetimidate donor in chloroform under silver triflate promotion. It is noted that such galactosylated anticancer nu cleosides may have improved biological specificity.