N-15-multilabeled adenine and guanine nucleosides. Syntheses of [1,3,NH2-N-15(3)]- and [2-C-13-1,3,NH2-N-15(3)]-labeled adenosine, guanosine, 2 '-deoxyadenosine, and 2 '-deoxyguanosine

We report a high-yield route to the following specifically N-15- and C-13-m ultilabeled nucleosides:[1,3,NH2-N-15(3)]- and [2-C-13-1,3,NH2-N-15(3)]-ade nosine; [1,3,NH2-N-15(3)]- and [2-C-13-1,3,-NH2-N-15(3)]-2'-deoxyguanosine. [1,3,NH2-N-15(3)]- and [2-C-13-1,3,NH2-N-15(3)]-2'-deoxyadenosine; [1,3,NH 2-N-15(3)]- and [2-C-13-1,3,-NH2-N-15(3)]-2'-deoxyguanosine. In each set, t he (13)C2 atom functions as a "tag" that allows the (15)N1 and (15)N3 atoms to be unambiguously differentiated from the untagged versions in N-15 NMR of RNA or DNA fragments. The key intermediate of this synthetic strategy fo r both the adenine and guanine nucleosides is [NH2, CONH2-N-15(2)]-5-amino- 4-imidazolecarboxamide. The [2-C-13]-label is added through a ring closure using [C-13]-sodium ethyl xanthate ((NaSCSOEt)-C-13). Enzymatic transglycos ylation of either multilabeled 6-chloropurine or multilabeled 2-mercaptohyp oxanthine and a final reaction with (NH3)-N-15 give the adenine and guanine nucleosides. This is the first report of a [3-N-15]-labeled guanine nucleo side.