Nucleoside 3′,5′-cyclic H-phosphonates, new useful precursors for the synthesis of nucleoside 3′,5′-cyclic phosphates and their analogues

摘要

Nucleoside H-phosphonates activated with a condensing agent spontaneously formed nucleoside 3′,5′-cyclic H-phosphonates. The cyclization was stereoselective and produced one of the P-diastereomers in preponderance (de ca. 80%). Nucleoside 3′,5′-cyclic H-phosphonates were stereochemically unstable and underwent epimerization affording the thermodynamically more stable diastereomer as a major product (de ca. 80%). They were susceptible to hydrolysis, transesterification, and oxidation and by changing oxidation protocols nucleoside 3′,5′-cyclic phosphate analogues, e.g. phosphodiesters, phosphorothioate diesters, and phosphotriesters, were obtained.