Studies on the Stereoselective Synthesis of Deuterated D-Ribose Derivatives

摘要

In view of the importance of the site-specific substitution of the H-atom by its stable isotope ~2H in a stereoselective/stereospecific manner at the pentose sugar residue, decreasing the spectralo overcrowding in various regions of 1D and 2D homo-and heteronuclear correlation spectra of oligo-DNA and -RNA, there is always a need for the development of new methods for the incorporation of ~2H at different sites of a ribose. High-yielding multistep syntheses of C(2)-, and (5R)-and (5S)-3,5-deuterated ribose derivatives have been envisaged for the application of site-specific incorporation of multilabeled nucleosides into oligomers to facilitate their structure elucidation by NMR spectroscopy. All syntheses started from D-glucose after proper derivatization. In the case of C(2), > 97 atom-% isotope was incorporated, employing an inversion of the configuration at C(2) as the key reaction. For C(5), two different routes were envisaged: on the one hand, deuterated achiral reagnet was treated with a conformationally locked sugar moiety 15. while, on the other, chiral protonated sources were used to transfer the H-atom to a C(5)-deuterated aldehyde 18. In all cases, enantiomeric and isotopic purities were found to be as high as > 97% as determined by NMR spectroscopy.