Synthesis of the Trisaccharide and Tetrasaccharide Moieties of the Potent Immunoadjuvant QS-21.

The title trisaccharide and tetrasaccharide moieties have been synthesized as part of our research programme to construct the complex triterpenoid saponin QS-21, a potent immunoadjuvant, which has been used in a series of clinical immunization trials. In view of the unwillingness of glucuronic acid as glycosyl acceptor, the branched glucuronic acid-containing trisaccharide 20 was synthesized from D-glucose, which was in turn glycosylated at positions 2 and 3, followed by oxidation at position 6, in a linear sequence of 15 steps and in good overall yield. The apiose-containing tetrasaccharide 36 was constructed by a linear glycosylation strategy from the non-reducing terminal sugar, D-apiose, which was prepared from D-xylose by a known procedure, also in a linear sequence of 15 steps. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.