Synthesis And Bioactivity Study Of Pyrazole Derivatives And A Novel Method For Preparation Of Highly Functionalized Furans

Pyrazoline derivatives are a class of five-membered nitrogen-containing heterocyclic compounds,presenting as an important structural element in some natural products and synthetic drugs.Pyrazoline derivatives have broad prospects in pharmaceutical industry.This class of compounds have also been demonstrated possessing important biological activities in the area of antipyretic,analgesic,anticoagulant,antidepressant,anti-hyperglycemia,antibacterial and anti-cancer.Tyrosinase,whose chemical essence is copper-containing protein,is prevalent in nature.It plays a key role in the biosynthesis of melanin,and in the rate-limiting enzyme of melanin formation.Tyrosinase associating with pigmented diseases and abnormal pigmentation is the main factor for the enzymatic browning of fruits and vegetables,which in turn,affects the immune growth of insects meanwhile.Therefore,the inhibition of tyrosinase activity is of great significance in the field of human skin pigment disease treatment,food preservation and agricultural insect resistance.This paper describes the synthesis of a class of new pyrazoline derivatives and studies on their activity as tyrosinase inhibitors and antitumor drugs.Furan ring as a typical representative of the five-membered heterocycle,widely exists in natural products,and this specific moiety continuously attracts the attention of organic chemists because of its inherent biological activities.Recent studies have revealed that multi-substituted bark compounds exhibit good antiviral,antibacterial,antitumor,anti-inflammatory and insecticidal activities.Furan derivatives can be used for the synthesis of many biologically active natural products as an class of important heterocyclic intermediates.In addition,they are also utilized as an important matrix precursor in synthetic chemistry,polymer chemistry and material chemistry.Therefore,the development of highly efficient and environment-friendly synthesis methods for the synthesis of multi-substituted furan compounds is rather desirable and of great importance.Visible light has the advantages of large natural storage,environmental friendly proterties,and great application potential,all of which make visible photocatalysis a powerful tool for organic synthesis.In this paper,a novel and efficient method is developed for the synthesis of highly functionalized dihydrofuran though a photoredox process under the irradiation of sunlight.This context mainly includes the following two parts:In the first part,pyrazoline derivatives were synthesized through the condensation of chalcones,thiosemicarbazide and 4-chlorophenylsemicarbazide in ethanol at room temperature in alkaline conditions.All of the synthetic compounds were subjected to tyrosinase inhibition assay with L-DOPA as substrate using kojic acid as positive control;in vitro cell viability assay was also carried out using the human mammary gland epithelial cell lines.In the second part,multi-substitution furans were obtained through the dimerizative annulation of β-carbonylketones under the visible-light-mediated aerobic condition in acetonitrile at room temperature using Ru(bpy)3Cl2 as catalyst.This practical and enviromental-friendly method has the advantages of high yield,high purity,and easy to handle.