207448-94-0Relevant academic research and scientific papers
Synthesis and Separation of Diastereomers of Ribonucleoside 5′-(α-P-Borano)triphosphates
He, Kaizhang,Hasan, Ahmad,Krzyzanowska, Bozenna,Shaw, Barbara Ramsay
, p. 5769 - 5773 (2007/10/03)
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′-(α-P-borano)triphosphates. Phosphitylation of the 2′,3′-protected ribonucleoside with 2-chloro4H-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, P2,P3-dioxo-P1-ribonucleosidylcyclotriphosphate 3. Immediate oxidation of compound 3 with amine·borane complex results in ribonucleoside 5′-(α-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′-(α-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′-(α-P-borano)triphosphate 6 is achieved by reverse phase HPLC.
