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

doi:10.1055/s-0035-1561637

Synthesis, Inhaltsverzeichnis

Synthesis 2016; 48(18): 3050-3056
DOI: 10.1055/s-0035-1561637

paper

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

Authors

Sarbjit Singh

^aCollege of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea eMail: ychoi@korea.ac.kr

^bCollege of Life Sciences and Biotechnology, Korea University, Seoul 02842, Republic of Korea
Veeraswamy Gajulapati

^bCollege of Life Sciences and Biotechnology, Korea University, Seoul 02842, Republic of Korea
Minkyoung Kim

^bCollege of Life Sciences and Biotechnology, Korea University, Seoul 02842, Republic of Korea
Ja-Il Goo

^bCollege of Life Sciences and Biotechnology, Korea University, Seoul 02842, Republic of Korea
Jae Kyun Lee

^cCenter for Neuromedicine, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
Kyeong Lee

^aCollege of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea eMail: ychoi@korea.ac.kr
Chong-Kyo Lee

^dVirus Research and Testing Center, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Republic of Korea
Lak Shin Jeong*

^eThe Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea eMail: lakjeong@snu.ac.kr
Yongseok Choi*

^bCollege of Life Sciences and Biotechnology, Korea University, Seoul 02842, Republic of Korea

Abstract

Alle Artikel dieser Rubrik

^§ These authors contributed equally to this work.

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.

Key words

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

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