A Divergent Approach for the Synthesis of d- and l-4′-Ethynyl Dioxolane Nucleosides with Potent Anti-HIV Activity

Sarbjit Singh, Veeraswamy Gajulapati, Minkyoung Kim, Ja Il Goo, Jae Kyun Lee, Kyeong Lee, Chong Kyo Lee, Lak Shin Jeong, Yongseok Choi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Novel 4′-C-ethynyl isomeric dioxolane nucleoside analogues (β-d, α-d, β-l, and α-l, respectively) are successfully synthesized via a divergent strategy from the common starting material, (Z)-but-2-ene-1,4-diol, and are characterized and evaluated for their anti-HIV-1 and anti-HIV-2 activities. The β-d and β-l products display potent in vitro activities against HIV-1 (IIIB) with EC50 values of 0.75 and 0.87 μM, respectively, and against HIV-2 (ROD) with EC50 values of 0.75 and 0.35 μM, respectively, being better in comparison with 3TC [EC50, 5.27 μM (HIV-1) and 1.30 μM (HIV-2)]. The β-d and β-l nucleosides also potently inhibit different drug-resistant strains of the HIV-1 virus (L100I, K103N, Y181C, and V106A). The selectivity indices and cytotoxic profiles of the β-d and β-l nucleosides are much better than those of the standard drugs AZT and d4T.

Original languageEnglish
JournalSynthesis (Germany)
DOIs
Publication statusAccepted/In press - 2016 Apr 13

Keywords

  • 4′-acetylene nucleosides
  • AIDS
  • anti-HIV
  • asymmetric synthesis
  • dioxolane nucleosides
  • divergent synthesis

ASJC Scopus subject areas

  • Organic Chemistry
  • Catalysis

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