Studies of Nucleosides and Nucleotides. Synthesis and Characterization of 8-Methyladenosine

Abstract

8-Methyladenosine (X) was synthesized by two ways starting from 2’,3’-0-isoprop-ylidene-2-methylthioinosine (I). The compound (I) was methylated with t-butyl hydroperoxide in acidic media in the presence of ferrous ion to give 8-methyl compound (II) in a yield of 46%. Raney nickel dethiolation of II and acetylation at 5’-OH followed by chlorination using SOCl2/DMF gave 6-chloro-8-methylpurine derivative (V). The compound (V) was treated with liq. NH3 and deprotected with trifluoroacetic acid to give 8-methyladenosine (X). Alternatively II was acetylated at 5’-OH, chlorinated with Vils-meyer-Haack reagent and treated with liq. NH3 to give 2’,3’-0-isopropylidene-2-methyl-thio-8-methyladenosine (IX). The compound (IX) was deacetonized and dethiolated with Raney nickel to give X. The physical properties of X was elucidated by ultraviolet, circular dichroism and nuclear magnetic resonance spectra. A syn type conformation was assigned to 8-methyladenosine. © 1977, The Pharmaceutical Society of Japan. All rights reserved.