Design And Synthesis Of Novel Sugar-functionalized Pillar[5]arene For Supramolecular Drug Delivery System

Small-molecule drugs have many adverse effects and generally suffer from poor solubility in aqueous media.Meanwhile,a lot of biological macromolecular drugs are easy to be hydrolyzed and have short half-lives,as well as have difficulty in passing through biological barriers.Supramolecular drug delivery systems(SDDSs)provide an effective way to solve these problems.Different from traditional drug delivery systems,SDDS are constructed by non-covalent bonds.Due to the dynamic properties of non-covalent interactions,the structure of the SDDSs can undergo reversible changes triggered by specific external stimuli(such as p H,temperature,light,enzymes and redox agents,etc.),thereby providing a platform for the design and development of functional and intelligent drug carriers.Supramolecular macrocyclic compounds are often used as building blocks for drug carriers.As a class of emerging supramolecular macrocyclic host,pillar[5]arenes have been used in the fields of chemistry,materials and life science,etc.Since the first report in 2008,they have been used a wide range of applications for their rigid scaffold,highly symmetric electron-rich cavity,and excellent physical and chemical properties.The rims of pillar[5]arenes can be modified with carboxylic and ammonium groups to make them water-soluble.These water-soluble derivatives have shown excellent biocompatibility and targeting ability for biomedical applications..However,the limited availability of water-soluble pillar[5]arenes becomes the bottleneck for their application in SDDSs.Saccharides are not only the main energy source for cells,but also play an important role in cell communication.Therefore,they are indispensable in the construction of targeted drug delivery systems.Introducing glycosyl groups on pillar[5]arenes can improve their biocompatibility and provide active targeting abilities via “sugar cluster effect”.In this thesis,novel rim-differentiated pillar[5]arenes decorated by glucose,galactose,mannose,glucosamine and galactosamine were designed and prepared,Their structures were fully characterized by nuclear magnetic resonance spectroscopy(NMR)and high-resolution mass spectrometry.According to the chemical shift and coupling constants of H at the C-1position in the NMR spectra,the glucose and galactose moieties modified on the pillar[5]arene were found to adopt the β configuration,while the mannose group has the α configuration.This study provides a new method to synthesize macrocycle-based scaffolds for the construction of SDDS.In addition,this thesis also covers a new solid-liquid extraction method to efficiently separate the rim-differentiated pillar[5]arene from the mixture of four constitutional isomers,further facilitating the application of such compounds in the construction of SDDS.Finally,this thesis explored the construction of novel metal-organic materials based on pillar[5]arene,and the synthesis of new type of “rim-differentiated”pillar[5]arenes in which the two rims of the P[5] macrocycles are decorated differently.The results of these studies enrich the case of this kind of research,which provides a reference.