Stereospecific synthesis of β-D-fructofuranosides using thioglycoside donors and internal aglycon delivery

Stereospecific synthesis of beta-D-fructofuranosides has been accomplished by the application of an internal acceptor delivery approach. The acceptor, ethanol or monosaccharides, is initially tethered to the fructofuranose 3-hydroxyl group, adjacent to the anomeric center and on the beta-side of the furanose ring, as part of a mixed p-methoxybenzaldehyde acetal, which is formed by DDQ-oxidation of ethyl 1,4,6-tri-O-benzyl-3-O-(4-methoxybenzyl)-2-thio-D-fructofuranoside in the presence of the acceptor or of the p-methoxybenzylated acceptor in the presence of the corresponding 3-OH fructofuranoside. Then, activation of the thioglycoside with a thiophilic promoter allows the delivery of the acceptor from the acetal to the activated anomeric center to yield the beta-linked fructofuranoside in high yields (76-85%). If promoters with nonnucleophilic anions (triflate, perchlorate) are used, the intermediate acetal decomposes to produce the beta-fructofuranoside products as 3-OH derivatives. However, if NIS is used as promoter, the N-succinimide anion interacts with the benzylidene carbon to give the beta-fructofuranoside products as mixed fructofuranoside-3-O-yl N-succinimide p-methoxybenzaldehyde acetals.