Rational design of naphthoquinone-based antibacterial agents through iridium-catalyzed enantioselective β-allenylation of 2-hydroxynaphthoquinones

Chakrabarty, A and Jaiswal, K and De, M and Mukherjee, S (2024) Rational design of naphthoquinone-based antibacterial agents through iridium-catalyzed enantioselective β-allenylation of 2-hydroxynaphthoquinones. In: Organic Chemistry Frontiers, 111 . pp. 5107-5115.

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Abstract

Against the backdrop of the established biological properties of 2-hydroxynaphthoquinone (lawsone) and related compounds, the rational design of chiral β-butyl lawsone derivatives as potential antibacterial agents, their enantioselective synthesis and investigation of their antibacterial properties are described. The synthesis is accomplished through enantioselective β-allenylation of 2-hydroxynaphthoquinones with allenylic alcohols under the cooperative catalysis of an Ir(i)/(phosphoramidite,olefin) complex and Lewis acidic La(OTf)3, followed by catalytic hydrogenation. In a rare example of the use of hydroxynapthoquinones in transition metal catalysis, β-allenylic lawsone derivatives are obtained generally in high yield with outstanding enantioselectivity (up to >99.9 : 0.1 er). The β-butyl lawsone derivatives, bearing a stereogenic center adjacent to the naphthoquinone core, showed high potency against Gram-positive bacterial strain MRSA (methicillin-resistant Staphylococcus aureus) with a minimum inhibitory concentration (MIC) as low as 1.5 μg mL�1 and low toxicity to mammalian cell lines such as HEK and HeLa. The bactericidal activity of these compounds is found to depend not just on the substituent at the stereocenter but also on their absolute configuration. © 2024 The Royal Society of Chemistry.

Item Type:	Journal Article
Publication:	Organic Chemistry Frontiers
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs to publisher.
Keywords:	Alcohols; Bacteria; Catalysis; Cell culture; Hydrogenation; Iridium compounds; Ketones; Mammals; Transition metals, Antibacterial properties; Biological properties; Cooperative catalysis; Enantioselective; Enantioselective synthesis; Lawsone; Naphthoquinones; Phosphoramidites; Rational design; Related compounds, Enantioselectivity
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	18 Oct 2024 11:51
Last Modified:	18 Oct 2024 11:51
URI:	http://eprints.iisc.ac.in/id/eprint/86409

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