Keywords: Chromenes, hydrazide, Suzuki-Miyaura coupling

Abstract: Being very important class of biologically active heterocyclic molecules, there is a need to synthesize novel derivatives of Chromenes (Benzopyrans) and Hydrozones. The developed synthetic route may pave the way for the discovery of new drugs for a variety of diseases. The project goal is to develop a reliable and efficient method for synthesizing this medicinally important class of heterocyclic molecules, such as 2H-chromes and their acetohydrazide-hydrazone derivatives, and to investigate their applications.

2H-Chromene derivatives were first synthesized from easily and cheaply available starting material Phenol. The reaction of phenol with acetonitrile in the presence of base led to Michael’s addition product which was subjected to hydrolysis to obtain an acid functional group. Reaction with Eaton’s reagent on this substrate led to ring formation giving rise to the 2H-Chroman-4-one product. The obtained 2H-Chroman-4-one was reacted with Vislmeier-Haack reagent to produce 4-chloro-3-formyl 2H-chromenes which served as the main structural unit for the synthesis of novel Functionalised 4-Phenyl-2H-chromene-3-carbaldehyde Hydrazones. The cross-coupling of aryl boronic acid with 4-chloro-3-formyl 2H-chromenes furnished the corresponding 4-aryl-3-formyl 2H chromenes in a chemo-selective way with good yields under Pd-catalyzed conditions. Further condensation with acetohydrazides yielded a variety of acetohydrazide-hydrazone derivatives of poly heteroaryl 3,4 disubstituted 2H-chromenes in good-high yields.

The acetohydrazide-hydrazone derivatives were then screened for various applications for both biological activities and photophysical properties. In silico studies have revealed that the newly synthesized series of Acetohydrazide-Aryl-Chromenes (AAC) are effective and selective inhibitors of α-amylase. This finding may pave the way for the synthesis of novel therapeutics for the management of diabetes and other conditions involving α-amylase activity. In order to fully comprehend the potential of these molecules as therapeutic agents, additional in vitro and in vivo studies are required. Along with biological activity, the synthesized molecules also gave very good results for photophysical properties which increases the scope for many more useful applications.

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