Stereochemistry of internucleotide bond formation by the H-phosphonate method. Part 6: Optimization of the reaction conditions towards highest stereoselectivity

The condensations of ribonucleoside 3′-H-phosphonates with simple alcohols and nucleosides are known to be stereoselective reactions that favour formation of DP(SP)-diastereomers of the produced H-phosphonate diesters without engaging any chiral auxiliaries. We have investigated various reaction conditions in order to attain the highest stereoselectivity for the condensation. With an optimal choice of solvents, reagent concentrations, temperature and the condensing agent used, the diastereomeric excess of the DP(SP)-isomers of dinucleoside H-phosphonates was enhanced from the initial 50–70% to ca. 85%.

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