The preparation and properties of O-methylated adenosine derivatives

Abstract

By reacting diazomethane with adenosine in a partially aqueous medium, 2'-O-methyladenosine, 3'-O-methyladenosine, 5'-O-methyladenosine, and 2',-3'-di-O-methyladenosine have been prepared in 38, 11, 1.5, and 3.5% yields, respectively. These yields are in general accord with the known mechanism of action of diazomethane and with the acidities of the individual hydroxyl groups of adenosine as determined by ion-exchange chromatography of the O-methylated derivatives on Dowex 1 (OH-) columns, i.e., the more acidic the hydroxyl groups, the greater the extent of methylation. Replacement of the 2'and/or 3'-hydroxyl group of adenosine by a methoxyl group slightly stabilized the glycosyl bond to acid-catalyzed hydrolysis. For 0.1 n HC1, 97.5°, the following first-order rate constants were determined: adenosine, 10 X 10-4 sec-1; 5'-0-^^/hile it is now clearly established that both tand rRNAs are frequently methylated at the 2'-oxygen of some of their ribose residues (Smith and Dunn, 1959; Singh and Lane, 1964a,b;Hall, 1964), our knowledge of the chemical behavior and biological significance of 2'-0-methyl nucleoside residues is, at best, fragmentary.Recent progress in methylating procedures (Broom and Robins, 1965; Khwaja and Robins, 1966) has made possible selective O methylation of adenosine and cytidine. Using the Broom and Robins (1965) procedure which employs diazomethane in aqueous dimethoxyethane, we have obtained on reaction of adenosine: 3'-O-methyladenosine, 5'-O-methyladenosine, and 2',-3'-di-O-methyladenosine in addition to the 2 '-0methyladenosine initially reported (Broom and Robins, 1965). These methylated adenosines can be readily separated by a combination of cellulose and anion-exchange chromatography making use, in the case of the latter technique, of the variation in acidity of the remaining hydroxyl groups of the derivatized adenosines (Dekker, 1965). In this paper we describe the isolation and properties of several methylated adenosines and their behavior toward (1) acid hydrolysis, (2) enzymatic deamination, and (3) the orcinol reaction.The preparation of 3'-O-methyladenosine has also been accomplished by the coupling of the appropriate

Aminoacyl derivatives of nucleosides, nucleotides, and polynucleotides. XIX. Nonisomerizable 2'- and 3'-O-aminoacyldinucleoside phosphates. Chemical synthesis and acceptor activity in the ribosomal peptidyltransferase reaction

“…However, the isomers were separated (Figure 1) on a Dekker column (Gin and Dekker, 1968). The nmr spectrum of each of the methyl derivatives Ilia and Illb showed no detectable contamination by the second isomer.…”

Amino acids are not all initially attached to the same position on transfer RNA molecules.

“…There is considerable asymmetry between the two hydroxyl groups in that the 2'-hydroxyl is more nucleophilic than the 3' and has a lower pK for dissociation of the hydroxyl group proton (9,10). It is well known, for example, that chemical acylation takes place more readily on the 2' rather than the 3' positions of ribonucleotides (9).…”

Synthesis of Fluorinated Nucleosides

“…However, because 2′‐acyl derivatives are unstable with respect to their 3′‐isomers, subsequent equilibrium results in acetyl migration, with the 3′‐ O ‐acylate being obtainable by crystallization from the equilibrium mixture (Brown et al, ; Reese and Trentham, ; Johnston, ; Reese et al, ). The acidity of the 2′‐OH group explains this tendency (Brown and Robins, ; Gin and Dekker, ). In this manner, the 3′‐ O ‐benzoates ( S.2, S.3 ) can be isolated from mix tures of the 3′‐ and 2′‐isomers.…”