I. Synthesis of aryl alpha-C-glycosides of mannose as bacterial anti-adhesins. II. Chelating ligands of tricyclo[7.5.0.0(2,8)]tetradecane system.

摘要

Several synthetic methodologies for synthesis of aromatic α-C-glycosides of mannose have been explored. (1R/S)-2,6-anhydro-3,4,5,7-tetra-O-benzyl-1-C-(4 ′methoxy)phenyl-D-glycero-D-galacto -heptitol were prepared from a glycosyl cyanide approach, where 2,3,4,6-tetra-benzyl-α-D-mannopyranosyl cyanide was converted into the corresponding α-aldehyde, and subsequently coupled with p-methoxyphenyl magnesium bromide. On the other hand, the reduction of 2,3,4,6-tetra-benzyl-α-D-mannopyranosyl cyanide provided 2,3,4,6-O-benzyl-α-D-mannopyranosyl amiomethane, which was a precursor for α-D-mannopyranosyl phthalimidomethane, and α-D-mannopyranosyl 2′,3′-pyridinecarboxyimidomethane. Single crystal X-ray diffraction analysis indicated that α-D-mannopyranosyl phthalimidomethane adopted the expected “exo-anomeric” conformation in the solid state, and there were two different rotamers along the C6–C7 bond.; The Grignard reaction approach provides a short route to the aromatic α-C-glycosides of mannose. Low yield of C-glycoside was observed when 6-O-acetyl-3,4,6-tri-O-benzyl-α-D-mannopyranosyl bromide was used as substrate. The reaction of 2-O-acetyl-3,4,6-tri-O-benzyl-α-D-mannopyranosyl bromide with p-methoxybenzyl magnesium chloride in THF gave 3,4,6-tri-O-benzyl-α-D-mannopyranosyl 4′-methoxyphenylmethane in good yield. However, 1,2-O-(1-benzylethylidine)-3,4,6-tri-O-benzyl-β-D-mannopyranose was isolated as major product when the same bromide was treated with benzylmagnesium chloride in ether.; Both α-D-mannopyranosyl phenylmethane and α-D-mannopyranosyl phenylpropane could be synthesized from tri-O-acetyl-D-glucal and organozinc reagents in three steps. Unfortunately, the reactions of tri-O-caetyl-glucal and organozinc reagents such as o-ClBnZnBr, p-(COOMe)BnZnBr, p-tBuBnZnBr and m-PhBnZnBr could not provide clean α-C-glycosides.; Finally, the Suzuki coupling approach was used to generate aromatic α-C-glycosides of mannose with different structural types. The substrates, 3,4,6-tri-O-benzyl-α-D-mannopyranosyl ethylene and 2,3,4,6-tetra-O-benzyl-α-D-mannopyranosyl propane, were successfully coupled with 4-iodoanisole in modest yield.; The rotator distribution around the C1–C7 bond of the α-C-glycoside of mannose has been studied. All the C-glycosides of mannose adopt mainly the Gt. conformation in solution, a similar shape as the corresponding O-glycosides. This similarity provides the structural background to use C-glycoside as bacterial anti-Adhesins.