PREPARATION AND PROPERTIES OF O-METHYLATED ADENOSINE DERIVATIVES

By reacting diazomethane with adenosine in a partially aqueous medium, 2′-O-methyIadenosine, 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 × 10-4 sec-1; 5′-O-methyladenosine, 10 × 10-4 sec-1; 3′-O-methyladenosine, 7.5 × 10-4 sec-1; 2′-O-methyladenosine 6.0 × 10-4 sec-1; and 2′,3′-di-O-methyladenosine, 3.5 × 10-4 sec-1. Methylation also affects the rate of color development in the orcinol reaction. Relative to adenosine, the following color yields were obtained using standard conditions (6 N HC1, 20 min at 100°): 2′-O-methyladenosine, 23%; 3′-O-methyladenosine, 100%; 5′-O-methyladenosine, 125%; and 2′,3′-di-O-methyladenosine, 15%. These values provide further evidence regarding the chemical basis of the orcinol test. Adenosine deaminase from calf intestinal mucosa was found to be inactive toward 5′-O-methyladenosine but active toward the derivatives bearing methyl groups on the 2′- and/or 3′-oxygens. © 1968, American Chemical Society. All rights reserved.