Chemical Modification of Nucleic Acid Components: Reactions of Cytosine, Cytidine, Isocytosine, and Adenine with Methyl N-Cyanomethanimidate

Article abstract of DOI:10.1021/jo00320a043

Reaction products of cytosine, cytidine, isocytosine, and adenine with methyl N-cyanomethanimidate (1) are reported.Thus, the reactions of cytidine and cytosine with 1 yielded (6,7-dihydro-6-oxo-7-β-D-ribofuranosyl-4H-pyrimido<1,6-a>-1,3,5-triazin-4-ylidene)guanidine (4) and (6,7-dihydro-6-oxo-4H-pyrimido<1,6-a>-1,3,5-triazin-4-ylidene)guanidine (5), respectively.The interrelationship between the two compounds was established by deribosidation of 4.The reaction of 1 with isocytosine gave two isomeric products: (6-oxo-6H-pyrimido<1,2-a>-1,3,5-triazin-4-yl)guanidine (9) and (8-oxo-8H-pyrimido<1,2-a>-1,3,5-triazin-4-yl)guanidine (10).The two products were differentiated by several means, including dehydrative cyclization of 9.Adenine and 1 also gave three products: N⁶-<(cyanoamino)methylene>adenine (21) and two fluorescent isomers, (7H-1,3,5-triazino<2,1-i>purin-7-ylidene)guanidine (20) and (9H-1,3,5-triazino<2,1-i>purin-9-ylidene)guanidine (22).The structures of the products were established by 1H and 13C NMR, IR, UV, and mass spectral analyses and, where necessary, by unequivocal syntheses.The source of the incorporation of a cyanamide unit into the structures of the final products (e.g., 4, 5, 9, 10, 20, and 22) was explored by studying the behavior of the reagent 1 toward nucleophiles, e.g., H2O (D2O), and by isolation of the major byproducts of the reactions.The fluorescence spectral data for the final compounds are also reported.The compounds from isocytosine, 9 and 10, and one from adenine, 22, exhibit exceptionally large Stokes shifts.