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)

Occurrence, Synthesis and Biosynthesis of Bacterial Heptoses

“…Subsequent acetylation, osmylation and periodate cleavage gave 14, which was deprotected to afford the known methyl L-glycero--D-manno-heptopyranoside 15 in 53% yield (based on methyl mannoside 11) [86]. Intermediate 14 was finally implemented into the strategy for the preparation of a 2,3-disubstituted and a 3-monosubstituted heptoside needed for the synthesis of lipooligosaccharides from Neisseria gonorrhoeae 15253 [87,88]. A similar masked oct-7-enopyranosyl precursor of heptose was also installed in a synthetic scheme leading to a 3,4-disubstituted heptose moiety [89].…”

Synthesis of a Spacer-Linked Derivative of Heptopyranosyl(α1-3)heptopyranose Expressed in Lipooligosaccharide and Lipopolysaccharide

“…Finally, 2,3 and 3,4-substituted Hep derivatives can be converted from methyl 2-O-benzyl-mannoenopyranoside as described in the past. 3,14) This versatile compound could therefore be fully utilized for the synthesis of partial structures containing branched Hep structures expressed in LOS. The structures of all the compounds synthesized in this work were rigorously characterized by 1 H-and 13 C-NMR analyses.…”