Premium
Expanding the Genetic Alphabet: Pyrazine Nucleosides That Support a DonorDonorAcceptor Hydrogen‐Bonding Pattern
Author(s) -
von Krosigk Ulrike,
Benner Steven A.
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490120
Subject(s) - chemistry , riboside , oligonucleotide , stereochemistry , pyrazine , acceptor , hydrogen bond , ring (chemistry) , derivative (finance) , base pair , ribose , dna , molecule , enzyme , organic chemistry , biochemistry , physics , financial economics , economics , condensed matter physics
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.