Action of trimethyl phosphate on ribonucleosides in aqueous solution

Abstract

The action of trimethyl phosphate (TMP) on adenosine (A), cytidine (C), guanosine (G), and uridine (U) has been examined in homogeneous aqueous solution at pH 7–12.5 and 37–50°. All these nucleosides underwent methylation reactions, showing the following reactivity order; methylation sites are indicated in parentheses. At pH 7: C (N-3)≳ G (N-7) > A (N-1) > U (N-3); at pH 8.5–10: U (N-3) > G (N-1 > N-7 > O-6) > A [N-1 > 2′(3′)-OH] > C (N-3). At pH >11, the carbohydrate hydroxy-groups were also methylated to provide O²′- and O³′-methylated nucleosides. These results are discussed in terms of a useful alkylating procedure for the aqueous phase as well as a method for selectively modifying nucleic acids. The use of TMP as an additive for commercial products is also considered briefly.