Substituted 3-E-Styryl-2H-chromenes and 3-E-Styryl-2H-thiochromenes: Synthesis, Photophysical Studies, Anticancer Activity, and Exploration to Tricyclic Benzopyran Skeleton

Abstract

A series of densely substituted 2H-chromenes and 2H-thiochromenes were synthesized in good yield through cyanuric chloride-dimethylformamide mediated cleavage of different spiro-4-hydroxychroman-3,1'-cyclopropanes and similar thiochroman analogues. This protocol involves operationally very simple, facile and cost-effective reactions using easily accessible reagents under mild reaction condition with tolerance of a variety of sensitive moieties. Results of steady state and time-resolved absorption and emission spectroscopy highlighted the potential of these compounds as fluorescence probes and designated the suitability for subcellular bioimaging. The prepared 2H-chromenes demonstrated profound cytotoxic activity against MCF-7 cell line. DFT calculations were done on a representative compound where the results indicated promising reactivity of the title compounds as electron-donating dienes. As a continuation, some of these compounds underwent [4 + 2] Diels-Alder cycloaddition with electron-deficient dienophiles in the absence of any activator or catalyst, which provided an easy access to an array of hitherto unreported molecular frameworks related to bioactive cannabinoid skeletons. These newly constructed Diels-Alder adducts also bear substantial antiproliferative properties.

Synthesis and antiproliferative activity of sulfa-Michael adducts and thiochromenes derived from carbohydrates

“…2 Moreover, preparation of new 2Hthiochromenes is an active area of research 3 because of the recent finding of their anticancer activity. 4 Although there have been different methods describing the preparation of thiochromanes or thiochromenes, 1 their asymmetric synthesis either by using optically pure starting materials 5 or chiral auxiliaries 6 are rather scarce. In most cases, the initial step in the mechanism of their formation is a conjugate addition of thiols to electron-deficient olefins or a sulfa-Michael addition, 6f-h and the second process is a nitroaldol reaction.…”

Convenient and Highly Efficient Routes to 2 H‐Chromene and 4‐Chromanone Derivatives: Iodine‐Promoted and p‐Toluenesulfonic Acid Catalyzed Cascade Cyclizations of Propynols

“…The well‐known synthetic route to 2 H ‐chromenes is by the cyclization of substituted phenolic propargyl ether compounds,6 whereas the classical methods for preparing 4‐chromanones involve the condensation cyclization of carbonyl compounds with o ‐hydroxyacetophenones5b, 7 and the addition reaction to 4 H ‐chromen‐4‐ones 8. With the persistent efforts of many chemists, adequate evolutions have been achieved on the synthesis of both types of essential molecular scaffolds 2f–i. 3a,e,f, 9, 10 Nevertheless, the development of efficient and straightforward methods in a simple operation and under mild conditions is still fueled by the strong and growing aspiration for such processes in most areas of chemical synthesis.…”

The Advances and Applications of Arynes and Their Precursors to Synthesize the Heterocyclic Compounds: A Review

“…Whereas, three or more substituted arenes are widespread in natural products and medicines [3,22,23]. Breaking this two site bonding restriction of an aryne intermediate could provide synthetic chemists a broader spectrum of means in terms of constructing multi-substituted arenes for the purpose of quick [24,25].…”