Expanding the Genetic Alphabet: Pyrazine Nucleosides That Support a DonorDonorAcceptor Hydrogen‐Bonding Pattern

The 6‐aminopyrazin‐2(1 H )‐one, when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond donordonoracceptor pattern to a complementary DNA or RNA strand. When paired with the corresponding acceptoracceptordonor purine in oligonucleotides, the heterocycle selectively contributes to the stability of the duplex, presumably by forming a base pair of WatsonCrick geometry joined by a nonstandard H‐bonding pattern, expanding the genetic alphabet. Reported here is a short, high yielding, β ‐ D ‐selective synthesis of a 6‐aminopyrazin‐2(1 H )‐one nucleoside via the glycine riboside derivative 28 . The key steps include a WittigHorner reaction of an appropriately protected ribose derivative ( Scheme 10 , 19 → 21 ) followed by a Michael ‐like ring closure ( Scheme 12 , 30 → 1a and 32 → 1b ). Thus, a variety of pyrazine nucleosides ( Scheme 13 ) including the target 6‐aminopyrazin‐2(1 H )‐one riboside 1a , and its 5‐methyl derivative 1b , 6‐amino‐5‐methylpyrazin‐2(1 H )‐one riboside, are obtained.