Discrimination of the two diastereoisomeric glycosides heterodendrin and epi-heterodendrin by the combined use of NOE and molecular mechanics

The two glycosides (S)-heterodendrin and (R)-epi-heterodendrin were synthesized in a novel, one-step enzymatic synthesis, and separated by means of column chromatography. The 1H NMR spectra of the two diastereoisomers differ mainly in the chemical shift of H-2′ of the side chain. At first sight the 1H NMR spectra do not allow a stereospecific assignment. It was found, however, that the NOE between the anomeric proton H-1 and H-2′ of the side chain is considerably larger in epi-heterodendrin than in heterodendrin, which indicates on a time-averaged basis a smaller distance between these two protons in epi-heterodendrin. This difference in conformational behaviour is correctly reproduced by molecular mechanics calculations, thereby offering a method for the discrimination of these two glycosides.