title: Synthesis of novel aza-analogues of tiazofurin with 2-[5,5-bis(hydroxymethyl)pyrrolidin-2-yl] framework as sugar mimic.
abstract: The novel aza-analogues of tiazofurin (TZF) with 2-[5,5-bis(hydroxymethyl)pyrrolidin-2-yl] moiety, as sugar mimic, were synthesized from O,O-cyclohexylidene derivative of 4,4-bis(hydroxymethyl)-4-nitrobutanal in multi-gram scale. The synthetic route consisted of three stages: (i) the synthesis of corresponding derivative of 5,5-bis(hydroxymethyl)pyrrolidine-2-carbonitrile, (ii) the construction of ethyl thiazole-2-carboxylate part by the conversion of the pyrrolidine-2-carbonitrile into the N-trifluoroacetyl derivative followed by cyclocondensation with L-cysteine ethyl ester and then by dehydrogenation, and (iii) the final transformation of the ethyl thiazole-4-carboxylate into the aza-analogues of TZF. The TZF aza-analogues were evaluated for their antiviral activities in cell-culture-based assays.
authors.affiliation: Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland. emirpuch@ch.pw.edu.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Mironiuk-Puchalska
authors.forename: Mariola
authors.initials: M
authors.lastname: Koszytkowska-Stawińska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Sas
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002241:Carbohydrates / Q000138:chemical synthesis / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry; D004267:DNA Viruses / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D018716:Molecular Mimicry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D001372:Aza Compounds; D002241:Carbohydrates; D011759:Pyrrolidines; C031752:ethyl cysteine; D012254:Ribavirin; D003545:Cysteine; C033706:tiazofurin