Synthesis and Separation of Diastereomers of Ribonucleoside 5'-(alpha-P-Borano)triphosphates.

Journal Article (Journal Article)

Nucleoside boranophosphates, in which one of the phosphate oxygens is replaced by a borane group, are isoionic and isoelectronic analogues of naturally occurring nucleotides. Boranophosphates also are biochemically important congeners of phosphorothioates and methylphosphonates. We have developed a convenient one-pot method to synthesize the set of ribonucleoside (A, U, G, and C) 5'-(alpha-P-borano)triphosphates. Phosphitylation of the 2',3'-protected ribonucleoside with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one gives the 5'-phosphite intermediate 2 which undergoes in situ substitution in the presence of pyrophosphate to give the cyclic intermediate, P(2),P(3)-dioxo-P(1)-ribonucleosidylcyclotriphosphate 3. Immediate oxidation of compound 3 with amine.borane complex results in ribonucleoside 5'-(alpha-P-borano)cyclotriphosphate 4. Subsequent reaction of compound 4 with water followed by ammonium hydroxide yields the crude product as a diastereomeric mixture of ribonucleoside 5'-(alpha-P-borano)triphosphate 6. Pure compound 6 is isolated in 30-45% overall yield using ion-exchange chromatography. The separation of two diastereomers of ribonucleoside 5'-(alpha-P-borano)triphosphate 6 is achieved by reverse phase HPLC.

Full Text

Duke Authors

Cited Authors

  • He, K; Hasan, A; Krzyzanowska, B; Shaw, BR

Published Date

  • August 1998

Published In

Volume / Issue

  • 63 / 17

Start / End Page

  • 5769 - 5773

PubMed ID

  • 11672174

Electronic International Standard Serial Number (EISSN)

  • 1520-6904

International Standard Serial Number (ISSN)

  • 0022-3263

Digital Object Identifier (DOI)

  • 10.1021/jo972002g


  • eng