Crystal packing in three related disaccharides: precursors to heparan sulfate oligosaccharides

Abstract

The three title compounds form part of a set of important precursor dissacharides which lead to novel therapeutics, in particular for Alzheimer's disease. All three crystallize as poorly diffracting crystals with one independent molecule in the asymmetric unit. Two of them are isostructural: 4-methoxyphenyl 4-O-[6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-4-O-(9-fluorenylmethyloxycarbonyl)-α-d-glucopyranosyl]-2-O-benzoyl-3-O-benzyl-6-O-chloroacetyl-α-l-idopyranoside, C59H56ClN3O16, (I), the ido-relative of a reported gluco-disaccharide [Gainsford et al., 2013). Acta Cryst. C69, 679–682] and 4-methoxyphenyl 4-O-[6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-4-O-(9-fluorenylmethyloxycarbonyl)-α-d-glucopyranosyl]-2-O-benzoyl-3-O-benzyl-6-O-methoxyacetyl-α-l-idopyranoside, C60H59N3O17, (II). Both exhibit similar conformational disorder of pendant groups. The third compound 4-methoxyphenyl 4-O-[6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-α-d-glucopyranosyl]-2-O-benzoyl-3-O-benzyl-6-O-methoxyoacetyl-β-d-glucopyranoside, C52H55N3O15, (III), illustrates that a slightly larger set of weak intermolecular interactions can result in a less disordered molecular arrangement. The molecules are bound by weak C—H...O(ether) hydrogen bonds in (I) and (II), augmented by C—H...π interactions in (III). The absolute configurations were determined, although at varying levels of significance from the limited observed data.

Keywords

• crystal structure
• disaccharide
• Alzheimer's
• synthesis
• hydrogen bonding
• C—H...π contacts