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

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.

通过氰尿酰氯-二甲基甲酰胺（cyanuric chloride-dimethylformamide）介导的不同螺-4-羟基色满-3,1′-环丙烷及类似硫代色满类似物的裂解反应，以优异收率合成了一系列高度取代的2H-色烯（2H-chromenes）与2H-硫代色烯（2H-thiochromenes）。该合成工艺操作简便易行、成本低廉，所用试剂易于获取，反应条件温和，且对多种敏感官能团具有良好的耐受性。稳态及时间分辨吸收发射光谱的测试结果表明，此类化合物具备作为荧光探针的应用潜力，适用于亚细胞生物成像。所制备的2H-色烯对MCF-7细胞系展现出显著的细胞毒活性。研究选取代表性化合物进行密度泛函理论（DFT）计算，结果显示目标化合物作为给电子二烯体具备优异的反应活性。在此基础上，部分化合物可与缺电子亲双烯体发生[4+2]狄尔斯-阿尔德（Diels–Alder）环加成反应，且无需任何活化剂或催化剂，该路线可便捷获取一系列迄今未报道的、与具有生物活性的大麻素骨架相关的分子骨架。这些新构建的狄尔斯-阿尔德加合物同样具备显著的抗增殖活性。