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

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.