SYNTHESIS OF SITE-SPECIFIC DEUTERIUM SUBSTITUTED METHYL 6-O-[(R)-1-CARBOXYETHYL]-ALPHA-D-GALACTOPYRANOSIDE AND (S)-1-CARBOXYETHYL]-ALPHA-D-GALACTOPYRANOSIDE AND CONFORMATIONAL-ANALYSIS THEREOF BASED ON J-COUPLINGS

Methyl 6-(S)-H-2-6-O-[(R)- and (S)-1-carboxyethyl]-alpha-D-galactopyra noside have been synthesized from 6-(S)-H-2-1,6-anhydro-beta-D-gaiacto pyranoside. Conformational analysis of the exocyclic dihedral angles h as been performed based on (3)J(H,H) and (3)J(C,H) coupling constants of the title compounds together with their non-deuterated counterparts . The omega dihedral angle (O-5-C-5-C-6-O-6) can be described by a con formational equilibrium where the order of conformers is gauche-trans > trans-gauche > gauche-gauche, i.e., the same as for galactose but wi th a different population distribution. The C-5-C-6-O-6-C-2' torsion p opulates only the gauche states, as deduced from J couplings. This is at variance with previous Langevin dynamics simulations in which the p roportion 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 compa tible with experimental data, although previous simulations have indic ated gauche conformers to be preferred. Since about half the number of the possible conformational states for the major degrees of freedom a re significantly populated, as corroborated by experimental data, the flexibility of the substituting l-carboxyethyl group is large. (C) 199 8 Elsevier Science Ltd. All rights reserved.