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

Abstract

The O^2′ = O^3′ isomerization of uridine 2′/3′-methylphosphonates, 2′/3′-isopropyl phosphates and 2′/3′-(2-ethoxyethyl) phosphates has been studied in buffer solution. In imidazole buffers, all these isomerizations exhibit only weak general acid catalysis. This low susceptibility of isomerization to buffer catalysis appears to be an inherent property of this reaction, and not a consequence of competitive buffer-catalyzed breakdown of the phosphorane intermediate to 2′,3′-cyclic phosphate: uridine 3′-(2-ethoxyethyl) phosphate and 3′-isopropyl phosphate exhibit a similar susceptibility of isomerization to buffer catalysis in spite of the fact that the former undergoes concurrent buffer-catalyzed cleavage and the latter does not. In carboxylic acid buffers (pH < 3), the 2′/3′-methylphosphonates were observed to undergo another buffer-catalyzed isomerization, which was first order in the concentration of both hydronium ion and the buffer acid. Plausible mechanistic interpretations for the buffer-catalyzed isomerizations are described.