Synthesis of C-5' chirally deuterated nucleosides with 100% optical purity.
The syntheses of chirally pure (5R)- and (5S)-[5-2H1]-D-ribose and (5R)-(5-2H1)-3-C-methyl-D-ribose and the syntheses of chirally pure (5'R)- and (5'S)-[5-2H1]-adenosine and (5'R)-[5'-2H1]-3'-C-methyladenosine are described. The 1H-NMR characteristics of these nucleosides and the mechanism of the reaction of adenosine and thionyl chloride-hexamethyl phosphoric triamide (HMPA) are also described. The stereospecific presence of deuterium in these nucleosides permits specific assignments for the resonances of 5'-protons. From the observed spin-spin coupling between H5' and H4', the estimates have been made of the rotamer population of the exocyclic 5'-carbinol groups of these nucleosides. It is shown that these nucleosides exist in gauche-gauche rotamer (ca. 70%) in aqueous solution. The SN2 mechanism of the chlorination reaction is suggested.
D003903:Deuterium; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D009705:Nucleosides / Q000138:chemical synthesis*
D007202:Indicators and Reagents; D009705:Nucleosides; D003903:Deuterium