Synthesis of novel 8-substituted carbocyclic analogs of 2',3'-dideoxyadenosine with activity against hepatitis B virus.
Synthesis and antiviral activity of several new 8-substituted carbocyclic analogs of D-2',3'-dideoxyadenosine are described. The new 8-substituted analogs were synthesized via lithiation of carbocyclic 2',3'-dideoxyadenosine followed by quenching with electrophiles. This methodology allows for a divergent synthesis of a variety of 8-substituted analogs from carbocyclic 2',3'-dideoxyadenosine in high yields. 8-Methyl and 8-halogenated carbocyclic 2',3'-dideoxyadenosine analogs showed 6-25 fold more activity against hepatitis B virus than the unsubstituted carbocyclic D-2',3'-dideoxyadenosine.
Gudmundsson
Kristjan S
KS
Division of Chemistry, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. kristjan.s.gudmundsson@gsk.com
Daluge
Susan M
SM
Condreay
Lynn D
LD
Johnson
Lance C
LC
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000254:growth & development; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D000998:Antiviral Agents; D016048:Dideoxyadenosine