Study On The Development Of New Methods For The Synthesis Of Benzodiazepine And Indenopyrazole Derivatives

As important nitrogen-containing heterocycles,benzodiazepine and indenopyrazole not only exist widely in nature,but also possess significant biological and pharmacological activities.Therefore,how to quickly and efficiently construct these nitrogen-containing heterocyclic skeletons is one of the important research topics of synthetic chemistry.On the other hand,propargyl alcohols are valuble bifunctional compounds with unique and diverse reactivities,and have thus been frequently used in the construction of carbocyclic and heterocyclic scaffolds.Based on the above background,some new methods for the synthesis of benzodiazepines and indenopyrazoles were developed in this thesis by using propargyl alcohols as versatile substrates and by taking advantages of transition metal-catalyzed inert carbon-hydrogen bond functionalization as a novel synthetic strategy.The thesis mainly includes the following two parts:Part Ⅰ: A simple and efficient method for the synthesis of pyrazolone fused benzodiazepines was developed.With this method,pyrazolinone fused benzodiazepines were efficiently synthesized from1-phenylpyrazolidine-3-ones and propargyl alcohols via Rh（III）catalyzed inert C（sp2）-H bond activation and [4 + 3] cyclization.Notably,this is the first example in which propargyl alcohol acted as a C3（not C2 or C1）synthon to react with 1-phenylpyrazolidinone to form a fused（spiro）seven-membered heterocyclic skeleton.This method has the advantages of easy-to-obtain substrates,high atom-economy and regioselectivity.Part Ⅱ: An efficient and novel method for the synthesis of indenopyrazolopyrazolones was developed.With this method,indenopyrazolopyrazolones were prepared from aryl azomethine imines and propargyl alcohols via ruthenium-catalyzed inert C（sp2）-H bond activation and the following cascade reactions it initiated.To our knowledge,this is the first example in which propargyl alcohol concurrently acted as both C2 and C1 synthons to participate in the formation of the indeno and the pyrazolyl units.In addition,biological activity screening of the products revealed that many of them possess significant anticancer activity,thus demonstrating their potential for pharmaceutical applications.In conclusion,some new methods for the synthesis of pyrazolone fused benzodiazepines and indenopyrazolopyrazolones have been developed in this thesis through systematic studies.Compared with literature methods,the protocols presented herein have the advantages of broad substrate scope,high efficiency and atom-economy,and simple operational procedures.