Boat conformations: Synthesis, NMR spectroscopy, and molecular dynamics of methyl 4,6-O-benzylidene-3-deoxy-3-phthalimido-α-d-altropyranoside derivatives

Addition of the elements of phthalimide to methyl 2,3-anhydro-4,6-O-benzylidene-α-d-mannopyranoside (1) under fusion conditions has yielded methyl 4,6-O-benzylidene-3-deoxy-3-phthalimido-α-d-altropyranoside (2). The conformation of the pyranose ring of 2 has been shown to be non-chair by 1H NMR spectroscopy, in contrast to the conformations of related derivatives having smaller substituents at C-3. Molecular dynamics simulations of 2 in explicit chloroform-d solvent have indicated four principal conformational possibilities. Of these, the 7C5/1S5 chair/skew boat form 2d has the lowest potential energy, and is largely consistent with the observed vicinal 1H–1H NMR coupling constants.