Purine studies. Part XX. Methylation and reduction of 2,8-dioxo-, 2,8-diamino-, and 2-amino-8-oxo-purines, and the stereochemistry of their 1,4,5,6-tetrahydro-derivatives

Abstract

Methylation of 1,7-dihydro-9H-purine-2,8-dione, 2 8-diaminopurine, and 2-amino-7,9-dihydropurin-8-one in neutral medium gave 3,7,8,9-tetrahydro-1,3,9-trimethyl-2,8-dioxo-2H-purinium iodide, 2,8-diamino-1,7,9-trimethyl-9H-purinium di-iodide, and 2-amino-7,9-dihydro-7-methylpurin-8-one respectively. Methylation of the 2,8-dione and its 1-methyl derivative in alkaline medium in each case provided a 1 : 1 mixture of 1,7-dihydro-1,3,7-trimethyl-3H- and 1,7-dihydro-1,7,9-trimethyl-9H-purine-2,8-dione, which on further methylation in neutral medium gave 3,7,8,9-tetrahydro-1,3,7,9-tetramethyl-2,8-dioxo-2H-purinium iodide. Methylation of 1,7-dihydro-7-methyl-9H-purine-2,8-dione, obtained by nitrosation of 2-amino-7,9-dihydro-7-methylpurin-8-one, in alkaline medium gave a 1 : 9 mixture of the above trimethylpurinediones. The methylation patterns were established by reduction, hydrolytic cleavage, methylation with CD₃I, and mass and ¹H n.m.r. spectral comparisons.

Reduction of these and related methylated purines with sodium borohydride produced 1,3,7-, 1,3,9-, and 1,7,9-trimethyl- and 1,3,6,9- and 1,3,7,9-tetramethyl-cis-perhydropurine-2,8-diones, and 1,7,9-trimethyl- and 1,6,7,9-tetramethyl-cis-2,8-diamino-4,5,6,9-tetrahydro-1H-purinium salts. Tafel's purone (perhydropurine-2,8-dione) and 2,8-diamino-4,5,6,9-tetrahydro-1H-purine were formed by electrolytic reduction of the respective purines, and had the cis-configuration at C-4 and C-5, similar to the above reduced purines, as shown by the patterns of ¹H n.m.r. signals, and spectral comparisons with cis-perhydrocyclopenta[d]pyrimidin-2-one and cis-2-amino- 4,4a,5,6,7,7a-hexahydro-3H-cyclopenta[d]pyrimidine.