Synthetic Studies of Imidazole C-Nucleosides toward Biofunctional Molecules

Abstract

  Synthetic studies of C4-linked imidazole C-nucleosides toward biofunctional molecules are described, in which the following items are covered. 1) Stereoselective synthesis of imidazole C- and pyrazole C-nucleosides via diazafulvene intermediates. 2) Synthesis of tetrahydrofuranylimidazoles using a PhSe group efficiently and its application to the new human histamine H₃ receptor (hH₃R) agonist, imifuramine, and the first selective human histamine H₄ receptor (hH₄R) agonist, OUP-16. 3) Synthesis of imidazole ribonucleoside phosphoramidite (Imz-PA) with pivaloyloxymethyl (POM) group for probing the catalytic mechanism of ribozymes. 4) Synthesis of a two-carbon-elongated homologue (Imz-C₂-PA) with a combination of POM and 2-cyanoethyl groups. 5) Incorporation of C₂-imidazole nucleoside into position 638 of VS ribozyme using Imz-C₂-PA and catalytic activities of the thereby generated modified VS ribozyme (G638C₂Imz).