title: Synthesis and antibacterial activity of 5'-tetrachlorophthalimido and 5'-azido 5'-deoxyribonucleosides.
abstract: Reported is an efficient synthesis of adenyl and uridyl 5'-tetrachlorophthalimido-5'-deoxyribonucleosides, and guanylyl 5'-azido-5'-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5'-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5'-hydroxyl with an azido group. The resulting compounds were converted to 5'-amino-5'-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2',3'-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5'-tetrachlorophthalimido and 5'-azido demonstrated increased antibacterial effect.
authors.affiliation: a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Van Ostrand
authors.affiliation: a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Jacobsen
authors.affiliation: a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Delahunty
authors.affiliation: a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
authors.forename: Carley
authors.initials: C
authors.lastname: Stringer
authors.affiliation: a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Noorbehesht
authors.affiliation: a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
authors.forename: Haidi
authors.initials: H
authors.lastname: Ahmed
authors.affiliation: a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Awad
mesh_terms: D000241:Adenosine / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D003853:Deoxyribonucleosides / Q000138:chemical synthesis / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008826:Microbial Sensitivity Tests; D009345:Neisseria meningitidis / Q000187:drug effects; D010797:Phthalimides / Q000737:chemistry; D014529:Uridine / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D001386:Azides; D003853:Deoxyribonucleosides; D010797:Phthalimides; D000241:Adenosine; D014529:Uridine
keywords: 2′,3′-O-isopropylidene nucleosides; 5′-Amino nucleosides; antibacterial activity of nucleoside analogs; mitsunobu reaction; modified nucleoside; ribonucleic guanidine