Studies Directed toward the Synthesis of Polysialogangliosides: The Regio- and Stereocontrolled Synthesis of Rationally Designed Fragments of the Tetrasialoganglioside GQ1b

Article abstract of DOI:10.1021/jo00032a601

The synthesis of suitably protected fragments of the tetrasialoganglioside GQ_1b (I), i. e., 1 (αNeuAc2->8αNeuAc2->3βGal1->4Glc), 2 (αNeuAc2->8αNeuAc2->3Gal), 3 (GalNAc), 4 (αNeuAc2->8NeuAc), 5 (βGal1->3GalNAc), and 42 <βGal1->3βGalNAc1->4(αNeuAc2->3)βGal->4Glc>, is described.All are rationally designed so that the protecting groups can be regioselectively introduced and removed, as needed, before or after the stereoselective coupling of an appropriate pair of fragments.The syntheses of 1, 2, and 4 all feature stereoselective glycosylations by glycosyl donors that bear a C-3 thiophenoxy stereocontrolling auxiliary.Compound 3 was prepared from the D-glucosamine derivative 17 by way of a novel intramolecular nucleophilic displacement with inversion of configuration.Furthermore, model glycosylations of 4-hydroxygalactose derivatives, in which the thioglycoside 3 and the fluoride 40 served as glycosyl donors, were performed.The reaction of 3 with the glycosyl acceptor 30 gave the disaccharide 31 (GalNAcβ1->4Gal), whereas that of 40 with 41 afforded the pentasaccharide 42.