Synthesis of site-specific deuterium substituted methyl 6-O-[(R)- and (S)-1-carboxyethyl]-α-d-galactopyranoside and conformational analysis thereof based on J couplings

Methyl 6-(S)-2H-6-O-[(R)- and (S)-1-carboxyethyl]-α-d-galactopyranoside have been synthesized from 6-(S)-2H-1,6-anhydro-β-d-galactopyranoside. Conformational analysis of the exocyclic dihedral angles has been performed based on 3JH,H and 3JC,H coupling constants of the title compounds together with their non-deuterated counterparts. The ω dihedral angle (O-5–C-5–C-6–O-6) can be described by a conformational equilibrium where the order of conformers is gauche-trans> trans-gauche> gauche-gauche, i.e., the same as for galactose but with a different population distribution. The C-5–C-6–O-6–C-2′ torsion populates only the gauche states, as deduced from J couplings. This is at variance with previous Langevin dynamics simulations in which the proportion of the trans state is significant. For the C-6–O-6–C-2′–H2′ torsion an equal population of the three staggered conformers is compatible with experimental data, although previous simulations have indicated gauche conformers to be preferred. Since about half the number of the possible conformational states for the major degrees of freedom are significantly populated, as corroborated by experimental data, the flexibility of the substituting 1-carboxyethyl group is large.