The synthesis of oligoribonucleotides. Part X. Preparation of 2′,3′-cyclic phosphates of ribonucleosides and diribonucleoside phosphates via phosphotriester intermediates

Abstract

Both 2′,5′-bis-O-4-methoxytetrahydropyran-4-yluridine (1a) and 2,5′-bis-O-4-methoxytetrahydropyran-4-yluridylyl-(3′→ 5′)-2′-O-4-methoxytetrahydropyran-4-yluridine o-chlorophenyl ester (7a) were converted into their diphenyl phosphate esters [(3) and (7b), respectively] by treatment with diphenyl phosphorochloridate in the presence of 5-chloro-1-methylimidazole (2). These phosphotriester derivatives, which were isolated in good yields, were converted into the corresponding mono- and di-nucleotide phenyl esters [(4a) and (8a), respectively] by alkaline hydrolysis. The latter compounds were treated with dilute acid (to remove the methoxytetrahydropyranyl groups) and the products were then treated with base, under very mild conditions, to give good yields of uridine 2′,3′-cyclic phosphate (5) and the dinucleoside phosphate cyclic phosphate (9), respectively.