Septanose Carbohydrates:Synthesis and Conformational Studies of Methyl alpha-D-glycero-D-Idoseptanoside and Methyl beta-D-glycero-D-Guloseptanoside

摘要

We report the synthesis of methyl alpha-D-glycero-D-idoseptanoside(1)and methyl beta-D-glycero-D-guloseptanoside(2)and the characterization of their preferred solution conformations by computational chemistry and ~1H NMR ~3J_(H,H)coupling constant analysis.Central to the synthetic approach was the epoxidation of glucose-derived oxepine 3 using DMDO.Nucleophilic attack on the resulting 1,2-anhydroseptanose using NaOCH_3 in CH_3OH followed by deprotection provided the 1,2-trans diastereomers 1 and 2.The computational approach for determining the preferred low energy septanose conformations began with a pseudo Monte Carlo search for each isomer using minimization with the AMBER force field.Single-point energy calculations(HF/6-31G and B3LYP/ 6-31+G)as well as full geometry optimizations in a model for aqueous solvent were then conducted using the conformers within 5 kcal/mol of the AMBER global minimum.Calculated ~3J_(H,H)values,based on a Boltzmann distribution of the computed low energy conformers,were compared to experimental ~3J_(H,H)values from ~1H NMR coupling constant analyses.The correlation between calculated and observed values suggest that septanose carbohydrates are not so flexible and should generally prefer one twist-chair(TC)conformation.