Synthesis of a 2,3‐Di‐O‐Substituted Heptose Structure by Regioselective 3‐O‐Silylation of a 2‐O‐Substituted Heptose Derivative.

Abstract

A 3,4-diol derivative of 2-O-benzyl (Bn) heptose (Hep), methyl 6,7-di-O-acetyl-2-O-benzyl-L-glycero-α-D-manno-heptopyranoside (3), was treated with both triethylsilyl (TES) and tert-butyldimethylsilyl (TBDMS) chlorides to regioselectively form the 3-O-silyl ethers 4 and 6, respectively. To examine whether silylation of the 3,4-diol of a 2-O-substituted disaccharide also gives the corresponding 3-O-silylated disaccharide, we synthesized α-GlcN3-(1⇄2)-Hep 11a by coupling a Hep 2-OH acceptor 9 with a GlcN3 trichloroacetimidate 10. As expected from the results obtained using the 2-O-Bn Hep 3, treatment of α-GlcN3-(1⇄2)-Hep-3,4-diol 14 with TESCl followed by acetylation gave only the 3-O-TES 15. Compound 14 was converted into the 3-OH acceptor 16 by silylation/acetylation — without isolating 15 — and subsequent acid hydrolysis. By coupling the disaccharide 3-OH acceptor 16 with per-O-benzylated β-lactosyl trichloroacetimidate 17, we obtained the desired 2,3-branched tetrasaccharide, α-Lac-(1⇄3)-[α-GlcN3-(1⇄2)]-Hep 18a. Hydrogenation of 18a, followed by N-acetylation, gave α-Lac-(1⇄3)-[α-GlcNAc-(1⇄2)]-Hep 22. Thus, we synthesized the 2,3-dibranched Hep by utilizing the 2-O-substituted Hep. This regioselective O-3-silylation of the 2-O-substituted Hep provides an intermediate that can be utilized for the synthesis of not only 2,3- and 3,4-dibranched Hep but also the 2,3,4-tribranched Hep structures present in lipooligo- and lipopolysaccharides produced by pathogenic Gram-negative bacteria. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)