New AZT Analogues Having 5′-Alkylsulfonyl Groups: Synthesis and Anti-HIV Activity

Al‐Masoudi, Najim A.; Al‐Soud, Yaseen A.; Ali, Ibrahim A. I.; Schuppler, Thilo; Pannecouque, Christophe; Clercq, Erik De

doi:10.1080/15257770701257178

Cited by 8 publications

(5 citation statements)

References 16 publications

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“…To our delight, a diverse array of p -substituted phenyl sulfinates, encompassing -methyl, -chloro, -bromo, -nitro, and -cyano groups, demonstrated excellent tolerance, yielding the desired products in yields from good to excellent ( 17 - 21 ). Furthermore, aliphatic sulfinates ( 22 and 23 ) also proved to be compatible which exhibited strong application potentials in pharmaceutical area such as the modification of azidothymidine which is known as an anti-HIV drug 66 . The adaptability of our methodology extended further to sulfinates bearing biphenyl-, cyclopropane-, and thiophene-groups.…”

Section: Resultsmentioning

confidence: 99%

Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes

Zhang,

Rabeah,

Das

2024

Nat Commun

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Controlling regioselectivity during difunctionalization of alkenes remains a significant challenge, particularly when the installation of both functional groups involves radical processes. In this aspect, methodologies to install trifluoromethane (−CF3) via difunctionalization have been explored, due to the importance of this moiety in the pharmaceutical sectors; however, these existing reports are limited, most of which affording only the corresponding β-trifluoromethylated products. The main reason for this limitation arises from the fact that −CF3 group served as an initiator in those reactions and predominantly preferred to be installed at the terminal (β) position of an alkene. On the contrary, functionalization of the −CF3 group at the internal (α) position of alkenes would provide valuable products, but a meticulous approach is necessary to win this regioselectivity switch. Intrigued by this challenge, we here develop an efficient and regioselective strategy where the −CF3 group is installed at the α-position of an alkene. Molecular complexity is achieved via the simultaneous insertion of a sulfonyl fragment (−SO2R) at the β-position. A precisely regulated sequence of radical generation using red light-mediated photocatalysis facilitates this regioselective switch from the terminal (β) position to the internal (α) position. Furthermore, this approach demonstrates broad substrate scope and industrial potential for the synthesis of pharmaceuticals under mild reaction conditions.

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Section: Resultsmentioning

confidence: 99%

Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes

Zhang,

Rabeah,

Das

2024

Nat Commun

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“…Furthermore, aliphatic sulfinates (22 and 23) also proved to be compatible which exhibited strong application potentials in pharmaceutical area such as the modification of azidothymidine which is known as an anti-HIV drug. 64 The adaptability of our methodology extended further to sulfinates bearing biphenyl-, cyclopropane-, and thiophene-groups. These substrates smoothly underwent difunctionalization reactions under the irradiation of red light, yielding products in the range of 35-93% (24)(25)(26).…”

Section: Substrate Scopementioning

confidence: 93%

Red Light-Mediated Photoredox Catalysis Promotes Regioselective Switch in the Difunctionalization of Alkenes

Das,

Zhang

2024

Preprint

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Controlling regioselectivity during difunctionalization of alkenes represents significant challenges, particularly when the installation of both functional groups is involved in radical processes. In this aspect, several functionalized trifluoromethylated (-CF3) compounds have been accomplished via difunctionalization reactions due to their wide importance in the pharmaceutical sectors, however, all these existing reports are limited to afford the corresponding β-trifluoromethylated products. The main reason for this limitation arises from the fact that -CF3 group served as an initiator in those reactions and predominantly preferred to be installed at the terminal (β) position of an alkene. In contrary, functionalization of the -CF3 group at the internal (α) position of alkenes provides valuable products but a meticulous approach is necessary to win this regioselectivity switch. Intrigued by this challenge, we have developed an efficient and highly regioselective strategy where -CF3 group is installed at the α-position of an alkene and at the end, molecular complexity is achieved via the simultaneous insertion of a sulfonyl fragment (-SO2R) at the β-position. This strategy provides the simultane-ous installation of two important functional groups such as -CF3 and -SO2R groups and both of these functional groups are the key units to attain or to enhance the bioactivity in organic molecules. A precisely regu-lated sequence of radical generation using red light-mediated photocatalysis facilitates this regioselective switch from the terminal (β) position to the internal (α) position. Furthermore, this approach demonstrates dis-tinctive regioselectivity, broad substrate scope and industrial potential for the synthesis of pharmaceuticals under mild reaction conditions.

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“…Compound 6 was also found to be cytoprotective with better selectivity index. Compound 7, a thiopropionic acid derivative also exhibited better activity against HIV-I (IC50 = 0.31) and HIV-2 (0.29 μg/ml) as well as cytoprotectivity (CC50 = 125 μg/ml) [23]. [24].…”

Section: Modifications At 5'-hydroxyl Groupmentioning

confidence: 99%

Zidovudine: Structural Modifications and Their Impact on Biological Activities and Pharmacokinetic Properties

Mohsin

Ahmed

Irfan

2019

J. Chil. Chem. Soc.

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Zidovudine was the first drug approved for the treatment of Acquired Immuno Deficiency Syndrome (AIDS). Its chemical name is azidothymidine (AZT). AZT use is associated with bone marrow toxicity. Shorter half-life and inability to penetrate the blood-brain barrier are the pharmacokinetic problems of this important drug molecule. Various modifications have been carried out in the structure of AZT. These include modification of hydroxyl and azido group, thymidine ring, preparation of phosphate and phosphonate derivatives, attachment of polymers and synthesis of hybrid molecules. Some of these changes produced compounds with significantly increased activity and less toxicity. This review highlights the various structural modifications of AZT and their influence on biological activities and pharmacokinetic properties.

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New AZT Analogues Having 5′-Alkylsulfonyl Groups: Synthesis and Anti-HIV Activity

Cited by 8 publications

References 16 publications

Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes

Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes

Red Light-Mediated Photoredox Catalysis Promotes Regioselective Switch in the Difunctionalization of Alkenes

Zidovudine: Structural Modifications and Their Impact on Biological Activities and Pharmacokinetic Properties

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