Synthesis Of Rare Heptose And Isoquinolinone Derivatives

Sugar compounds and isoquinolinone derivatives are important natural products which were distributed in the nature and have a wide range of biological activities.One of the main task of current drug chemistry is to synthesize and modify lead compounds with potential biological activities.Therefore,this paper is divided into two major parts,one is the synthesis of rare heptose,the another is about the new methods for synthesis of isoquinolinone derivatives.Sugar compounds are considered to be the starting materials for the construction of complex non-natural chiral molecules.One major task of sugar chemistry research is to use sugar to modify molecules with potential biological activity.Heptose,as a type of high-carbon sugar,is mainly distributed in plants,algaes and bacterias.Heptose has a wide range of biological activities,such as anti-inflammatory,anti-bacterial and anti-tumor.It can also treat hypoglycemia by inhibiting glucokinase.Therefore,it is of important significance to synthesize the heptose.This paper is concerned with the chemical synthesis of some rare heptose.A synthesis route of rare heptose has been established with cheap,readily available and abundant six-carbon sugars as starting materials.In this paper,we used D-(+)-mannose as raw material.Firstly,different protecting groups were used for selective protection and deprotection.Then,we used PCC to oxidize C-6 hydroxyl groups,after that,D-mannoseptene was obtained through the Wittig reaction.Finally,we used the AD-mix-α to give the corresponding heptose by sharpless dihydroxylation reaction.We also used D-(+)-glucose as the starting material for the synthesis of glucoheptose to confirm the general feasibility of this synthesis method.Isoquinolinone derivatives are one kind of alkaloids which were widely found in natural products.It has been found that these compounds have good activities of anti-HIV virus,anti-bacterial and anti-inflammatory.The synthesis of these compounds has always attracted much attention due to the unique biological activities.At present,the methods for synthesizing these compounds still have the shortcoming of high cost catalyst,complicated reaction conditions and low yields.Therefore,it is necessary to find some simpler,cheaper,and more efficient synthetic methods.The second part of this paper mainly explored two new methods for the synthesis of isoquinolinone derivatives.(1)This paper used N-alkyl(aryl)N-phenylbenzamide and benzyl alcohol as the starting materials.TBHP(tert-butyl peroxide)was used not only as an initiator,but also used as an oxidant.The reaction does not need any metal catalysis and only used ethyl acetate as a solvent.These corresponding isoquinolinone derivatives were obtained by reacting at 140°C for 24 hours.The method has the characteristics of simple reaction conditions,cheap raw materials and environmental friendliness.(2)In order to broaden the compatibility of the substrate,this article also used N-alkyl-N-phenylbenzamide and sodium benzenesulfinate as the starting material.For the first time,the paper reported a new method of using cheap and available catalytic systems of cobalt acetate catalyst,potassium iodide as an additive and acetonitrile as a solvent.The reaction is carried out at 140°C for 24 hours to give the corresponding products.This method can achieve high yields of regioselective products and have wide scope of application.This thesis explored a practical method for synthesizing rare heptose.The method has many advantages such as easiness to handle,simple reaction conditions,wide applicability scope and high potential industrial production value.At the same time,two new methods for the synthesis of isoquinolinone and its derivatives were developed in this thesis.Both of these synthetic methods exhibit the advantage of good substrate compatibility,simple operation,good yield and high regioselectivity.All synthesized sugar intermediates and isoquinolinone derivatives were determined and characterized by means of NMR,IR and HRMS.