Buffer-catalyzed interconversion of ribonucleoside 2 '/3 '-methylphosphonates and 2 '/3 '-alkylphosphates

The O-2' = O-3' isomerization of uridine 2'/3'-methylphosphonates, 2'/3'-is opropyl phosphates and 2'/3'-(2-ethoxy-ethyl) phosphates has been studied i n buffer solution. In imidazole buffers, all these isomerizations exhibit o nly weak general acid catalysis. This low susceptibility of isomerization t o buffer catalysis appears to be an inherent property of this reaction, and not a consequence of competitive buffer-catalyzed breakdown of the phospho rane intermediate to 2',3'-cyclic phosphate: uridine 3'-(2-ethoxyethyl) pho sphate and 3'-isopropyl phosphate exhibit a similar susceptibility of isome rization to buffer catalysis in spite of the fact that the former undergoes concurrent buffer-catalyzed cleavage and the latter does not. In carboxyli c acid buffers (pH < 3), the 2'/3'-methylphosphonates were observed to unde rgo another buffer-catalyzed isomerization, which was first order in the co ncentration of both hydronium ion and the buffer acid. Plausible mechanisti c interpretations-for the buffer-catalyzed isomerizations are described.