Synthesis of a 3,4-di-O-substituted heptose structure:: A partial oligosaccharide expressed in neisserial lipooligosaccharide

We have synthesized a tetrasaccharide containing a 3,4-dibranched L-glycero-D-manno-heptose (Hep), beta-lactosyl-(1-->4)-[L-alpha-D-Hep-(1-->3)]-L-alpha-D-Hep 19, by using a mannose (Man) derivative as an acceptor. Prior to the construction of the branched Hep, we confirmed that the 3,4-dibranched Man structure could be synthesized using a 3-branched Man 6 as an acceptor. Glycosylation of the acceptor 6 using hepta-O-acetyl-alpha-lactosyl trichloroacetimidate (7) gave the desired 3,4-dibranched structure, beta-lactosyi-(1-->4)-[alpha-Man-(1-->3)]-alpha-Man 8. As expected, beta-lactosyl-(1-->4)-[L-alpha-D-Hep-(1-->3)]-alpha-D-Man 14 was also obtained by glycosylating the 4-OH acceptor 13 with 7 in a similar manner. The Man residue of 14 was converted into the Hep unit by Swern oxidation, Grignard reaction, and oxidative cleavage followed by reduction. Thus, we constructed the 3,4-dibranched Hep structure 19 by using the 3-branched Man 13 as an acceptor. The current results demonstrate that the gauche orientation of the O-3 and O-4 units of the Man configuration does not prevent the formation of the 3,4-di-O-substituted structure. This approach should provide an alternative method to synthesize the 3,4-dibranched Hep structure expressed in LOS produced by pathogenic Gram-negative bacteria such as the Neisserial and Haemophilus species. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).