Nucleic Acid Related Compounds. 105. Synthesis of 2',3'-Didehydro-2',3'-dideoxynucleosides from Ribonucleoside Cyclic 2',3'-(Sulfates or Phosphates) or 2',3'-Dimesylates via Reductive Elimination with Sodium Naphthalenide(1).
Treatment of purine ribonucleosides with thionyl fluoride resulted in formation of cyclic 2',3'-sulfite esters. Acetylation of the 5'-hydroxy group and Sharpless oxidation (NaIO(4)/RuCl(3)) gave the cyclic 2',3'-sulfate ester derivatives. Treatment of 5'-O-silyl-protected ribonucleosides with thionyl chloride followed by oxidation gave an alternative route to the cyclic 2',3'-sulfates. Reductive elimination with sodium naphthalenide (THF/-50 degrees C) gave the 2',3'-unsaturated nucleosides. Parallel treatment of adenosine cyclic 2',3'-phosphate gave the 2',3'-olefin. The adenine, hypoxanthine, and 2-amino-6-methoxypurine 2',3'-didehydro-2',3'-dideoxynucleosides were prepared efficiently (40-60% overall yields of crystalline, analytically pure products; 3-5 steps, some combined into one-flask procedures) by treatment of 5'-O-protected 2',3'-di-O-mesylribonucleosides with sodium naphthalenide. Reactions were performed at or below ambient temperature with readily available reagents and standard laboratory conditions.
Robins
Morris J.
MJ
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602-5700.
Lewandowska
Elzbieta
E
Wnuk
Stanislaw F.
SF