Reduction of ribonucleosides to 2'-deoxyribonucleosides.
Ribonucleosides are converted into 2'-deoxyribonucleosides in good yields by a four-step procedure. Selective protection of the 3'- and 5'-hydroxyl groups with 1,3-dichloro-1,1,3,3-tetraisopropyl-1,3-disiloxane is followed by functionalization of the 2'-hydroxyl group with phenoxythiocarbonyl chloride. Free radical-mediated reductive C2'-O2' bond cleavage of these 3',5'-O-TPDS-2'-O-PTC-nucleoside derivatives with tributyltin hydride, followed by removal of the silyl protecting group with tetrabutylammonium fluoride, provides the 2'-deoxyribonucleosides. Adenosine, cytidine, guanosine, and uridine are converted into dA, dC, dG, and dU in overall yields of 60% to 80%. Use of tributyltin deuteride in the reductive cleavage step gives 2'-deuterio-2'-deoxyadenosine in 81% yield from adenosine with >85% retention of configuration at C2'. Application of this four-step protocol with nucleoside analogs is straightforward.
Robins
Morris J
MJ
Brigham Young University, Provo, Utah, USA.
Wnuk
Stanislaw F
SF
D003853:Deoxyribonucleosides / Q000138:chemical synthesis*; D005609:Free Radicals / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012263:Ribonucleosides / Q000737:chemistry*
D003853:Deoxyribonucleosides; D005609:Free Radicals; D012263:Ribonucleosides