New telluride-mediated elimination for novel synthesis of 2',3'-didehydro-2',3'-dideoxynucleosides.
Several 2',3'-dideoxynucleosides (ddNs) and 2',3'-didehydro-2',3'-dideoxynucleosides (d4Ns) are FDA-approved anti-HIV drugs. Via conveniently synthesized 2,2'-anhydronucleosides, we have developed a novel synthesis of d4Ns by discovering and applying a new telluride-mediated elimination reaction. Our experiment results show that after substitution of 2,2'-anhydronucleosides with a telluride monoanion, a telluride intermediate is formed, and its elimination leads to formation of the olefin products (d4Ns). Our mechanistic study indicates that this telluride-assisted reaction consists of two steps: substitution (or addition) and elimination. By using dimethyl ditelluride (0.1 equiv) as the reagent, d4Ns can be synthesized with yields up to 90% via this telluride-mediated elimination. Our novel strategy has great potential to simplify synthesis of these drugs and to further reduce cost of AIDS treatment and will also facilitate development of novel d4N and ddN analogues.
Sheng
Jia
J
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Hassan
Abdalla E A
AE
Huang
Zhen
Z
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism; D013691:Tellurium / Q000737:chemistry*
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D013691:Tellurium