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

The 6‐aminopyrazin‐2(1H)‐one, when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond donor? donor? acceptor pattern to a complementary DNA or RNA strand. When paired with the corresponding acceptor? acceptor? donor purine in oligonucleotides, the heterocycle selectively contributes to the stability of the duplex, presumably by forming a base pair of Watson? Crick 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(1H)‐one nucleoside via the glycine riboside derivative 28 . The key steps include a Wittig? Horner 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(1H)‐one riboside 1a , and its 5‐methyl derivative 1b , 6‐amino‐5‐methylpyrazin‐2(1H)‐one riboside, are obtained.