AMINOACYL NUCLEOSIDES .4. REARRANGEMENT OF N6-(ALPHA-AMINOACYL)ADENINES TO N-(6-PURINYL)AMINO ACIDS . APPLICATION TO ADENOSINE ANALOGS

Studies in the rearrangement of N6(α-aminoacyl)adenines into N-(6-purinyl)amino acids have revealed that N6-glycyl-9-methyladenine in aqueous solution undergoes facile transformation into a cyclic intermediate, 3-methyl-3H-imidazo-[2,1-i]purin-8-(7H)-one (5). This key intermediate, when heated in water or base, undergoes ring opening to give 1-carboxymethyl-9-methyladenine (6), which, on further heating in the same solution, rearranges into N-[6-(9-methylpurinyl)]glycine (7). The structure of the cyclic compound 5 has been confirmed by its synthesis from t-butyl-6-imino-9-methylpurine-1-acetate (11) and also from N6-chloroacetyl-9-methyladenine (9). The structures of 6 and 7 were verified by synthesis. The reaction products obtained from 5 under acidic, as well as neutral and alkaline, conditions are described. This study establishes that the 9-substituted N6-(α-aminoacyl)adenines undergo the rearrangement in a manner similar to that of the N6(α-aminoacyl)-adenines. © 1969, American Chemical Society. All rights reserved.