Acetylated methyl 1,2-dideoxyhex-1-enopyranuronates in density functional theory conformational studies

Geometry optimizations at the B3LYP level and single point calculations at the MP2 level are reported for the 4H5 and 5H4 conformations of methyl 3,4-di-O-acetyl-1,2-dideoxy-d-arabino-hex-1-enopyranuronate (methyl 3,4-di-O-acetyl-d-glucuronal), and methyl 3,4-di-O-acetyl-1,2-dideoxy-d-lyxo-hex-1-enopyranuronate (methyl 3,4-di-O-acetyl-d-galacturonal). Energy and geometry parameters are presented for the most stable optimized geometries. Conformational analysis of the acetoxy and methoxycarbonyl groups as well as the 1,2-unsaturated pyranoid ring is performed. It is demonstrated that both the acetoxy and methoxycarbonyl groups are planar and prefer cis over trans orientations with respect to the CO–O bond rotations. With regard to the AcO–R bond rotations some of the orientations are forbidden. The 4H5⇌⇌5H4 conformational equilibrium in both methyl 3,4-di-O-acetyl-d-glucuronal (shifted towards 5H4) and methyl 3,4-di-O-acetyl-d-galacturonal (shifted towards 4H5) is the outcome of the competition between the vinylogous anomeric effect and quasi 1,3-diaxial interactions. It is demonstrated that the orientation of the 4-OAc group influences the strength of the quasi 1,3-diaxial interactions between 3-OAc and 5-COOCH3 groups. Theoretical results are compared with assignments based on 1H NMR studies.

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► Energy parameters of the optimized glycals are presented.
► Favourable conformations of the acetoxy and methoxycarbonyl groups and glycal ring are demonstrated.
► Competition between the vinylogous anomeric effect (VAE) and quasi 1,3-diaxial interactions is discussed.
► Influence of the 4-OAc group on the conformational equilibrium is demonstrated.
► Comparison of the theoretical results with 1H NMR studies is performed.