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

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

Department of Biotechnology

Research output: Contribution to journal › Article › peer-review

6 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 language	English
Article number	ss-2016-f0124-op
Pages (from-to)	3050-3056
Number of pages	7
Journal	Synthesis (Germany)
Volume	48
Issue number	18
DOIs	https://doi.org/10.1055/s-0035-1561637
Publication status	Published - 2016 Sept 19

Bibliographical note

Funding Information:
This work was supported by a Korea University Grant (K1505491) and a grant of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) (No. 2014R1A2A2A01005455, 2012M3A9C1053532, and NRF-2015M3A6A4065734), Republic of Korea.

Keywords

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

ASJC Scopus subject areas

Catalysis
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1055/s-0035-1561637

Cite this

@article{b9b56f8788f643fe9e57805deb82118d,

title = "A Divergent Approach for the Synthesis of d - And l -4′-Ethynyl Dioxolane Nucleosides with Potent Anti-HIV Activity",

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.",

keywords = "4′-acetylene nucleosides, AIDS, anti-HIV, asymmetric synthesis, dioxolane nucleosides, divergent synthesis",

author = "Sarbjit Singh and Veeraswamy Gajulapati and Minkyoung Kim and Goo, {Ja Il} and Lee, {Jae Kyun} and Kyeong Lee and Lee, {Chong Kyo} and Jeong, {Lak Shin} and Yongseok Choi",

note = "Funding Information: This work was supported by a Korea University Grant (K1505491) and a grant of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) (No. 2014R1A2A2A01005455, 2012M3A9C1053532, and NRF-2015M3A6A4065734), Republic of Korea.",

year = "2016",

month = sep,

day = "19",

doi = "10.1055/s-0035-1561637",

language = "English",

volume = "48",

pages = "3050--3056",

journal = "Synthesis (Germany)",

issn = "0039-7881",

publisher = "Georg Thieme Verlag",

number = "18",

}

TY - JOUR

T1 - A Divergent Approach for the Synthesis of d - And l -4′-Ethynyl Dioxolane Nucleosides with Potent Anti-HIV Activity

AU - Singh, Sarbjit

AU - Gajulapati, Veeraswamy

AU - Kim, Minkyoung

AU - Goo, Ja Il

AU - Lee, Jae Kyun

AU - Lee, Kyeong

AU - Lee, Chong Kyo

AU - Jeong, Lak Shin

AU - Choi, Yongseok

N1 - Funding Information: This work was supported by a Korea University Grant (K1505491) and a grant of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) (No. 2014R1A2A2A01005455, 2012M3A9C1053532, and NRF-2015M3A6A4065734), Republic of Korea.

PY - 2016/9/19

Y1 - 2016/9/19

N2 - 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.

AB - 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.

KW - 4′-acetylene nucleosides

KW - AIDS

KW - anti-HIV

KW - asymmetric synthesis

KW - dioxolane nucleosides

KW - divergent synthesis

UR - http://www.scopus.com/inward/record.url?scp=84970044978&partnerID=8YFLogxK

U2 - 10.1055/s-0035-1561637

DO - 10.1055/s-0035-1561637

M3 - Article

AN - SCOPUS:84970044978

SN - 0039-7881

VL - 48

SP - 3050

EP - 3056

JO - Synthesis (Germany)

JF - Synthesis (Germany)

IS - 18

M1 - ss-2016-f0124-op

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this