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
Jl. Abad et al., 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, J ORG CHEM, 64(18), 1999, pp. 6575-6582
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.