title: Synthesis of novel deoxynucleoside S-methylphosphonic acids using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new equivalent of mercaptomethylphosphonate.
abstract: The synthesis of the novel nucleotide analogues 5'-deoxynucleoside-5'-S-methylphosphonates, starting from 5'-deoxy-5'-haloribonucleosides, 5'-O-tosylribonucleosides, and 2'-O-triflylnucleosides, is described. The phosphonothiolation of these compounds was achieved using S-(diisopropylphosphonomethyl)isothiouronium tosylate, a new, odourless, and efficient equivalent of mercaptomethylphosphonate. The thiolate anion of mercaptomethylphosphonate was generated in situ from the isothiouronium salt in both protic and aprotic solvents using two equivalents of sodium iso-propoxide. The prepared nucleoside 5'-S-methylphosphonates were deprotected, and the free phosphonic acids were transformed into diphosphoryl derivatives (the NTP analogues). Both mononucleotides and NTP analogues were studied as substrates/inhibitors of several enzymes that are involved in the nucleoside/nucleotide metabolism.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences v. v. i., Flemingovo 2, 166 10 Prague 6, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Kóšiová
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.forename: Natalya
authors.initials: N
authors.lastname: Panova
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis*; D014105:Tosyl Compounds / Q000737:chemistry*
chemical_list: D009705:Nucleosides; D009943:Organophosphorus Compounds; C559530:S-(diisopropylphosphonomethyl)isothiouronium tosylate; D014105:Tosyl Compounds; D007550:Isothiuronium; C032627:methylphosphonic acid