Functional Aromatic Heterocycle:Design, Synthesis And Performance Study

Aromatic heterocyclic compounds have a wide-ranging application vision in different fields of industry, agriculture and peoples’ daily life. Many important chemical materials, medicines, pesticides, explosives and dyes are aromatic heterocyclic compounds which have tremendous diversity. Herein my researches mainly focused on five- or six-membered aromatic heterocycles such as naphthalimide; dithienylethene and 1,3-oxazole and developed new applications in the directions of medicine, pesticide and photoelectric material.Naphthalimides have gained much attention recently in the area of applied chemistry and become a popular research direction. On the one hand, they can recognize or respond to the signals affecting or determining the properties of these molecules in nanometer scale and achieve the regulation and control to functions. On the other hand, they can supply biological tools and lead compounds with controllability, designability, affordability, diversity and chemical synthetic ability for biotechnology and drug discovery by regulating and controlling biological macromolecules, especially proteins.β-N-acetyl-D-hexosaminidase (EC 3.2.1.52) is a widely distributed enzyme that catalyzes the release of N-acetyl-β-D-glucosamine (GlcNAc) or N-acetyl-β-D-galactosamine (GalNAc) residues from the non-reducing ends of oligosaccharides and sugar components of glycoproteins and glycolipids. These enzymes are present in numerous species of diverse organisms, in which they play different physiological roles. Selective inhibition against β-N-acetyl-D-hexosaminidase is an effective method to regulate and control important physiological processes. Hence, this target has been paid much attention by many researchers from different areas. They hope fulfill the regulating of pathological and physiological processes which involve this enzyme by controlling the activity of this target. However, most of reported inhibitors possess carbohydrate scaffolds. Comparing with noncarbohydrate-based structure, it is more challenging to convert these leads of sugars into therapeutic agents because of poor pharmacokinetic properties and complex synthetic chemistry, in particular the difficulties in further optimization by medicinal chemistry.Firstly, a novel and efficient skeleton, which was unsymmetrical dyad containing naphthalimide and methoxyphenyl moiety with an alkylamine spacer linkage as noncarbohydrate-based inhibitor was synthesized and evaluated bioactivities against human β-N-acetyl-D-hexosaminidase. The most potent inhibitor exhibits high inhibition with Ki, values of 0.63 μM. The straightforward synthetic manners of these unsymmetrical dyads and understanding of the binding model could be advantageous for further structural optimization and development of new therapeutic agents for Hex-related diseases.Secondly, a series of noncarbohydrate-based inhibitors using naphthalimide as parent structure against of Hex2 was designed and synthesized. Comparing with traditional inhibitors, these structures possess their own characteristics with straightforward synthesis, low cost, steady chemical property and easy modification. Analysis of enzyme and inhibitor binding model based on tryptophane florescence titration, molecular modelling and docking provided platform for developing selective insecticide against asiatic corn borer. At the same time, the preliminary in vivo evaluation indicated these naphthalimide derivatives had good insecticide activities. This is aslo the first time insecticidal naphthalimides have been found.In order to develop selective inhibitors against Asiatic corn Borer β-N-acetyl-D-hexosaminidase and decrease the inhibition against human β-N-acetyl-D-hexosaminidase, we designed and synthesized a noncarbohydrate-based inhibitor with high selectivity targeting of Hexl. This inhibitor was formation of N,N-dimethylamino naphthalimide and 1,3,4-thiazole with an alkylamine spacer linkage. It could bind with of Hexl selectively and had no affect to the activity of human Hex. This structure is the first noncarbohydrate-based inhibitor against of Hexl and provide theory reference for developing green pesticides because of its high selectivity.In addition, a series of 2,5-disubstituted-1,3-oxazole derivatives were synthesized by a mercury(II) catalyzed intramolecular cyclization reaction as key step. The preliminary evaluation of synthesized compounds indicated that these structures exhibited good weight inhibitory activity and could be developed as novel environmental benign insect growth regulators.Besides, photoswith-fluorophore-conjugates bearing carboxylic acid group based on BODIPY dyes and dithienylethene were designed, synthesized and evaluated their steady state spectral performance. These conjugates could bind covalently to semiconductor or metal substrates to supply a model for interfacial electron transfer studies and open the ability to provide surfaces with reversible photoswitchable properties. Meanwhile, bicyclo[1.1.1]pentane and triazabicyclo[3.3.1]nonane were used as rigid linker between the dye and semiconductor for the first time. The photochemical property of the conjugate designed and synthesized based on this framework has been improved greatly.