Synthesis of a 3,4‐Di‐O‐Substituted Heptose Structure: A Partial Oligosaccharide Expressed in Neisserial Lipooligosaccharide.

Abstract

We have synthesized a tetrasaccharide containing a 3,4-dibranched L-glycero-D-manno-heptose (Hep), β-lactosyl-(1⇄4)-[L-α-D-Hep-(1⇄3)]-L-α-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-α-lactosyl trichloroacetimidate (7) gave the desired 3,4-dibranched structure, β-lactosyl-(1⇄4)-[α-Man-(1⇄3)]-α-Man 8. As expected, β-lactosyl-(1⇄4)-[L-α-D-Hep-(1⇄3)]-α-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. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)