Photocatalyzed Chemo‐Selective Alkylation of Quinones and Phenothiazinones with Alkyl Amides: Photophysical and Cytotoxic Activity Studies

Abstract

Alkylation of naphthoquinones (NQs) and phenothiazinone (PTZs) was achieved through chemo‐selective functionalization of different mono/di‐alkyl amides in the presence of photocatalyst eosin‐y and TBHP under the influence of blue light (Blue LEDs) as an energy source, at room temperature to get the products in moderate to good yield. These highly conjugated alkylated compounds displays absorption and emission in the visible region, has potential to be used as fluorescent probes and other light harvesting materials. Insilico study revealed that some of these compounds are potential phosphodiesterase‐4B (PDE4B) inhibitors and has excellent drug like properties. Furthermore, the cytotoxic activity of alkylated quinones toward human lung cancer cell line (A549) was studied.

Guggulsterone – a potent bioactive phytosteroid: synthesis, structural modification, and its improved bioactivities

“…[97][98][99][100] So this approach is an efficient way to quickly generate new chemical entities on a lead molecule without resorting to de novo synthesis. There are several late-stage diversification approaches in many natural products, such as estrone, 101 resveratrol, 102 artemisinin, 103 juglone, 104 bakuchiol, 105 vitamin K 3 , 106 and curcumin, 107 were reported in the literature.…”

Direct Functionalization of para‐Quinones: A Historical Review and New Perspectives

“…Later, in 2021, Ilangovan and co-workers investigated a photocatalyzed mono-and dialkylamidation of naphthoquinone using Eosin Y as a photosensitizer (Scheme 24). [64] Mechanistically, the shown reaction follows the single electron transfer (SET) and HAT processes for the alkylamidation of 1,4-naphthoquinones. Initially, excited Eosin Y cleaves TBHP to hydroxide anion and tert-butoxide radical through the SET process; consequently, tert-butoxide radical oxidizes the CÀ H bond of N-methyl amide to form tert-butanol and carboncentered N-methyl amide radical, which further adds to quinone to form the alkylated quinonyl radical.…”

“…Later, in 2021, Ilangovan and co‐workers investigated a photocatalyzed mono‐ and dialkylamidation of naphthoquinone using Eosin Y as a photosensitizer (Scheme 24). [64] …”

Direct C−H Radical Alkylation of 1,4‐Quinones

“…Shortly after, Ilangovan's group described a photocatalyzed version of this reaction, compatible with mono-and dialkylamides 32 (Scheme 16). [39] Eosin Y was used as a photosensitizer, generating upon blue LED photoexcitation tBuO * XI and Eosin Y + * via a single-electron transfer. Radical XI then undergoes HAT from the alkylamide.…”