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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)