Total synthesis of 2 ',3 ',4 ',5 ',5 ''-H-2(5)-ribonucleosides: The key building blocks for NMR structure elucidation of large RNA

The diastereospecific chemical syntheses of uridine-2',3',4',5',5 "-H-2(5) (21a), adenosine-2,3',4',5',5 "-H-2(5) (21b), cytidine-2',3',4',5',5 "-H-2( 5) H-2(5) (21c), and guanosine-2',3',4',5',5 "-H-2(5) (21d) (> 97 atom % H- 2 at C2', C3', C4', and C5/C5 ") have been achieved for their use in the so lution NMR structure determination of oligo-RNA by the Uppsala "NMR-window" concept (refs 4a-c, 5a, 6), in which a small H-1 segment is NMR-visible, w hile the rest is made NMR-invisible by incorporation of the deuterated bloc ks 21a-d, The deuterated ribonucleosides 21a-d have been prepared by the co ndensation of appropriately protected aglycone with 1-O-acetyl-2,3,5-tri-O- (4-toluoyl)-alpha/beta -D-ribofuranose-2,3,4,5,5'-H-2(5) (19), which has be en obtained via diastereospecific deuterium incorporation at the C2 center of appropriate D-ribose-H-2(4) derivatives either through an oxidation-redu ction-inversion sequence or a one-step deuterium-proton exchange in high ov erall yield (44% and 24%, respectively).