Septanose Carbohydrates:  Synthesis and Conformational Studies of Methyl α-d-glycero-d-Idoseptanoside and Methyl β-d-glycero-d-Guloseptanoside

Abstract

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.

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

“…We have also used 13 C chemical shifts as diagnostics for anomeric configuration of septanosides in previous systems. In the limited examples we have collected, 7,14,17,18 the trend is that d C1 of b-septanosides is slightly downfield relative to a-septanosides. The 13 C NMR measured values for d C1 of 3 is 106.1 ppm and that of 4 is 109.3 ppm.…”

“…The rationale draws significantly from our earlier analysis of methyl septanosides 1 and 2. 7 The chromatographic behavior of compounds 11 and 12, prepared by the epoxidation of oxepine 6 followed by methanolysis of the intermediate 1,2-anhydroseptanose, was reminiscent of the products of epoxidation/ methanolysis of the original oxepine 7. That is, the higher R f material was assigned as the a anomer in the original system and the lower R f material was assigned as the b with a product ratio of 1:3 a:b.…”

“…5 Other computational and spectroscopic investigations of monocyclic seven-membered ring systems (cycloheptane, oxepane as well as 1,3-and 1,4-dioxepane) have established some fundamental principles concerning conformation. [6][7][8][9] First, of the twist-chair (TC), chair (C), twist-boat (TB), and boat (B) conformations, the TC is nearly always the global low energy minimum. For the seven-membered rings of low symmetry, individual unique conformers are defined by adding super-and subscripts to the TC/C descriptors.…”

“…7 Our approach was based on the method originally developed on methyl a-D D-arabinofuranoside. 12 Briefly, a family of starting conformers were generated by a Monte Carlo search followed by AMBER minimization.…”

Tandem cyclization and acetalization of a homologated D-glucose delivers D-glycero-D-guloseptanosides

“…19 The H2 signal of 21α (in the α:β mixture) was identified by a combination of HSQC and COSY experiments. The 1 H signal for H1, which was in a section of the spectrum with many other overlapping signals, was located in the HSQC experiment.…”