Use of ¹³C as an Indirect Tag in ¹⁵N Specifically Labeled Nucleosides. Syntheses of [8-¹³C-1,7,NH₂- ¹⁵N₃]Adenosine, -Guanosine, and Their Deoxy Analogues

We have previously reported the use of a ¹³C tag at the C2 of ¹⁵N-multilabeled purine nucleosides to distinguish the adjacent-labeled ¹⁵N atoms from those in an untagged nucleoside. We now introduce the use of an indirect tag at the C8 of ¹⁵N7-labeled purine nucleosides. This tag allows unambiguous differentiation between a pair of ¹⁵N7-labeled purines in which only one is ¹³C8 labeled. Although the very small C8-N7 coupling (<1 Hz) precludes its direct detection in 1D ¹⁵N spectra, 2D ¹H-¹⁵N NMR experiments display the large C8-H8 coupling (>200 Hz) because H8 is coupled to both N7 and C8. The ¹³C8 atom is introduced by means of a ring closure of the exocyclic amino groups of a pyrimidinone using [ ¹³C]sodium ethyl xanthate. Here, we present methods for the syntheses of [8-¹³C-1,7,NH₂-¹⁵N ₃]adenosine, -guanosine, and their deoxy analogues.