Septanose carbohydrates: synthesis and conformational studies of methyl alpha-D-glycero-D-idoseptanoside and methyl beta-D-glycero-D-guloseptanoside.
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 (1)H NMR (3)J(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(3)OH 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 (3)J(H,H) values, based on a Boltzmann distribution of the computed low energy conformers, were compared to experimental (3)J(H,H) values from (1)H 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.
Dematteo
Matthew P
MP
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA.
Snyder
Nicole L
NL
Morton
Martha
M
Baldisseri
Donna M
DM
Hadad
Christopher M
CM
Peczuh
Mark W
MW
D002236:Carbohydrate Conformation; D020650:Combinatorial Chemistry Techniques; D008759:Methylglycosides / Q000138:chemical synthesis* / Q000737:chemistry*; D008962:Models, Theoretical; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013816:Thermodynamics
D008759:Methylglycosides