title: New neplanocin analogues. 7. Synthesis and antiviral activity of 2-halo derivatives of neplanocin A.
abstract: The syntheses and the antiviral activities of 2-halo derivatives of neplanocin A (1b,c), (6'R)-6'-C-methylneplanocin A (2b), and dehydroxymethylneplanocin A (3b,c) are described. SN2 reaction of the known cyclopentenyl units 12 and 13 with 2-haloadenines under basic conditions gave the protected carbocyclic nucleosides 14b,c and 15b,c, respectively. Starting from the cyclopentenone derivative 5, the optically active tosyloxycyclopentene derivative 11 was prepared, which was similarly condensed with 2-fluoroadenine to give the protected (6'R)-6'-C-methyl derivative 16b. Deprotection of these compounds afforded the target 2-halo derivatives of neplanocin A. Of these new compounds, 2-fluoroneplanocin A (1b) showed an antiviral potency and a spectrum that was comparable to that of neplanocin A (1a). It was particularly active against vaccinia virus, vesicular stomatitis virus, parainfluenza virus, reovirus, arenaviruses (Junin, Tacaribe), and human cytomegalovirus, i.e., those viruses that fall within the purview of the S-adenosyl-L-homocysteine hydrolase inhibitors.
authors.affiliation: Institute for Life Science Research, Asahi Chemical Industry Co., Ltd., Shizuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Obara
authors.forename: S
authors.initials: S
authors.lastname: Shuto
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001116:Arenaviridae / Q000187:drug effects; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000187:drug effects; D015394:Molecular Structure; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects; D012087:Reoviridae / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
chemical_list: C101621:2-fluoroneplanocin A; D000998:Antiviral Agents; C031096:neplanocin A; D000241:Adenosine