A new strategy for the synthesis of 3-arylisocoumarins and 8-hydroxy-3-arylisocoumarins was investigated by using acyl anion chemistry for the initial C-C bond formation. The obtained keto esters and keto lactones as intermediates underwent based-promoted intramolecular cyclization to afford 3-arylisocoumarins in good yields. The developed methodology was applied for the synthesis of the important natural products thunberginol A and cajanolactone A. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Indrapal Singh Aidhen

Department Of Chemistry

Kasireddy Sudarshan

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

European Journal of Organic Chemistry

We report the discovery of an anomalous reaction of 2-(alkynonyl)alkynylbenzenes under AgI catalysis for the selective formation of isocoumarins. This reaction is previously undocumented for 2-(alkynonyl)alkynylbenzenes in terms of the reaction mechanism and the product formed. Water (H2O18) labeling studies suggested a possible mechanistic pathway in which the initial formation of a pyrylium ion is followed by hydrative dealkynylation, that is, water incorporation and alkyne expulsion, similar to a retro-Favorskii reaction. © 2019 Wiley-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

Chemistry - An Asian Journal

An Unusual Conversion of 2-(Alkynonyl)Alkynylbenzenes to Isocoumarins by a Retro-Favorskii-like Degradation

A new route for the synthesis of 3-substituted and 8-hydroxy-3-substituted isocoumarins was developed by modified Julia olefination for initial C–C bond formation between aldehydes and benzylic sulfones. Palladium-catalyzed Meinwald rearrangement was used as a key step for the obtainment of ketone intermediates, which – upon base-promoted intramolecular cyclization – afforded the desired isocoumarins. The developed method paves the way to hitherto unknown 3-glycosylisocoumarins, in general, and 3-glucosylisocoumarins, in particular, wherein the glucosyl moiety is attached to the pyrone ring of the isocoumarin framework. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Convenient Synthesis of 3-Glycosylated Isocoumarins

The biosynthesis of leukotrienes in one of the arachidonic acid pathways and PGE2in the other by 5-LOX and mPGES1 respectively, play pivotal roles in augmenting inflammatory responses. PGE2is known to participate in cancer pathological processes as well. Isocoumarins are natural compounds with a wide range of biological activities. In this study, 3-aryl isocoumarin derivatives are synthesized and tested against 5-LOX enzyme in vitro and PGE2production in HeLa cells. Most of the compounds show high activity, and 1c is identified as a dual inhibitor with an IC50of 4.6 ± 0.26 μM and 6.3 ± 0.13 μM against 5-LOX and PGE2production respectively. Another compound 7f, exhibits an IC50of 12.4 ± 0.14 μM against 5-LOX. Further investigations reveal that the mechanism of action of 1c and 7f against 5-LOX is mixed and competitive modes of action respectively. Thunberginol (7c) exhibits IC50of 15.8 ± 0.03 μM against PGE2production. 1c and 7c inhibit the mRNA expression of mPGES1 and COX-2. The study has identified a novel scaffold, 1c with a dual inhibitory activity which can be further optimized to compete against Licofelone which is under clinical trials (with IC50of 6.0 μM for mPGES1 &amp; 0.2 μM for 5-LOX). To conclude, 3-aryl isocoumarin derivatives appears as promising tools to fight against inflammatory diseases as well as cancer. © 2016 Elsevier Masson SAS

European Journal of Medicinal Chemistry

Inhibition of the enzymes in the leukotriene and prostaglandin pathways in inflammation by 3-aryl isocoumarins

A new route based on the use of acyl anion chemistry was developed for the synthesis of (+)-centrolobine and its analogues. Acid-catalyzed benzylic cation initiated cyclization was the key step in the stereoselective formation of the cis-2,6-disubstituted tetrahydropyran ring. The developed methodology was applied to the synthesis of (+)-centrolobine analogues containing electron-donating substituents in the aryl rings. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Journal	Data powered by TypesetEuropean Journal of Organic Chemistry
Publisher	Data powered by TypesetWiley-VCH Verlag
ISSN	1434193X
Open Access	No