Conformational analysis of methyl 5-O-methyl septanosides: effect of glycosylation on conformer populations

Methyl 5-O-methyl-α-d-glycero-d-idoseptanoside (3) and methyl 5-O-methyl-β-d-glycero-d-guloseptanoside (4) were investigated as (1→5)-linked di-/oligoseptanoside mimetics. Here we report the synthesis of 3 and 4 and describe their preferred solution conformations through a combination of ab initio/DFT calculations and 1H 3JH,H NMR coupling constant analysis. The conformations of 3 and 4 observed in this study are discussed in comparison to those of the parent (C5 hydroxy) compounds 1 and 2. The results indicate that methyl 5-O-methyl-α-septanoside 3 is relatively rigid and adopts the same 3,4TC5,6 conformation as 1. Methyl 5-O-methyl-β-septanoside 4 is somewhat less rigid than its parent septanoside (2). In addition to the 6,OTC4,5 conformation adopted by 2, β-septanoside 4 also populates the adjacent 3,4TC5,6 conformation. Glycosylation at C5 on β-septanoside 4 therefore increases its overall flexibility and allows access to alternative ring conformations.