Studies of Phosphorylation. IV. The Phosphorylation of Nucleosides with Phosphorus Trihalide

Abstract

Abstract The treatment of a 2′,3′-O-isopropylidene nucleoside with phosphorus trichloride in the presence of trimethyl phosphate and subsequent hydrolysis gave a nucleoside 5′-phosphite in an excellent yield. Triaryl phosphates, trialkylphosphine oxides, and trialkyl phosphites were also found to be potential accelerators of the reaction. Their effects were comparable to that of trimethyl phosphate. The similar treatment of a 5′-O-acetyl nucleoside gave mixed nucleoside 2′- and 3′-phosphites in an approximate mole ratio of 4 : 6. The reaction intermediate, nucleoside phosphorodichloridite, was subjected to partial hydrolysis, giving the corresponding monochloridite. The product was readily oxidized to give the 5′-nucleotide. Chlorine was generally suitable as an oxidizing agent, but iodine gave better results for guanosine derivatives than did chlorine or bromine. The treatment of an unprotected nucleoside with phosphorus oxychloride in a trialkyl phosphate, prior to the reaction with phosphorus trichloride, could be used for the synthesis of a nucleoside 2′(or 3′),5′-diphosphate in a good yield.