Convenient synthesis of nucleoside borane diphosphate analogues: deoxy- and ribonucleoside 5'-P(alpha)-boranodiphosphates.
The nucleoside boranophosphates, having one of the nonbridging phosphate oxygens substituted with a borane (BH(3)) group, have shown potential therapeutical applications as aptamers, antisense agents, and antiviral prodrugs. An oxathiaphospholane approach, which does not require exocyclic amine protection of the nucleobase, has been successfully developed to efficiently synthesize 5'-P(alpha)-boranodiphosphates of 2'-deoxythymidine, adenosine, guanosine, and uridine. The approach involves a key intermediate, the borane complex of nucleoside 5'-O-1,3,2-oxathiaphospholane 16, that undergoes a ring-opening reaction catalyzed by 1,4-diazabicyclo[5.4.0]-undec-7-ene to form the protected nucleoside 5'-P(alpha)-boranodiphosphate 18. Treatment of 18 with ammonium hydroxide yielded diastereoisomeric mixtures of nucleoside 5'-P(alpha)-boranodiphosphates 5. This oxathiaphospholane approach ensures the availability of nucleoside 5'-P(alpha)-boranodiphosphate analogues needed for antiviral drug research.
Department of Chemistry, Box 90346, Duke University, Durham, North Carolina 27708-0346, USA.
Ping
P
Li
Barbara Ramsay
BR
Shaw
D001896:Boron Compounds / Q000138:chemical synthesis*; D003853:Deoxyribonucleosides / Q000737:chemistry*; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry*; D012263:Ribonucleosides / Q000737:chemistry*
D001896:Boron Compounds; D003853:Deoxyribonucleosides; D009705:Nucleosides; D010710:Phosphates; D012263:Ribonucleosides