Cyclodextrin-based Supramolecular Organogels And Design、Synthesis And Properties Of Functional Molecules

This dissertation includes three aspects:1) Novel heat-set supramolecular organogels based on cyclodextrin.2) Study on the design, synthesis and bio-activity of SGLT2inhibitors.3) Study on the design, synthesis and properties of heterocyclic conjugated molecules.The first chapter describes the study on cyclodextrin-based supramolecular organogels. In recent decades, the small molecular organogels drew attention for their application in drug delivery and smart materials. Traditional organogels has the reversible properties, of which the gel can be dissolved by heating and gelated by cooling. Here, we report two novel small molecular organogels. First, we identified a heat-set cyclodextrin-based gel which is formed with β-cyclodextrin, ps-An, and LiCl in DMF. This is a heat-set gel system which can turn into a clear solution upon cooling and is re-formed when heated to the gelling temperature. Commonly, ps-An and cyclodextrin can be dissolved easily in DMF, which is better in high temperature. However, we had an interesting observation that at a high temperature these molecules can self-assemble to form a gel.The organogels were characterized by optical microscopy (OM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The data indicates that the molecules in the system form fibers through hydrogen-bonds and complex. These are the main force for the formation of the gel and the temperature of gelation is regulated by the substituent group on ps-An. A mechanism is proposed and is supported by the results of molecular dynamics simulations.Another novel gel system that we report is a cyclodextrin-based temperature sensitive multiple-phase system. The gel is prepared with cyclodextrin and tetradecanol in DMAc. This circular system comprises four steps. First, the mixture dissolves to form clear solution and then becomes a gel by stirring. Upon heating to60℃, the gel turns to another clear solution. When increasing the temperature to120℃, white precipitates can be obtained. When cooling down to ambient temperature, the precipitate becomes the original clear solution. The circular step is repeatable. The traditional organic gel is a two-phase thermal reversible system on the basis of solution and gel, while this gel system is different. Some characterization data indicate that the aggregate mode of the gel is different from the precipitates. In the second chapter, we study the design, synthesis and bio-activity of SGLT2inhibitors. Our society and economy were burdened by dramatically increasing incidence of diabetes. Because the commercially available drugs to diabetes could not lower blood sugar and even brought about side effects, there are urgent needs in the fields of medicine to develop drugs that are highly effective and have low side effects. A new mechanism to restrict the blood pressure was brought up, with the deeper understanding of diabetes. Sodium glucose linked transporter2(SGLT2) can reabsorb more than90%glucose in kidney. By using SGLT2inhibitors, glucose will be secreted so that it lowers the level of blood sugar, which is a new target for synthesis of drugs. SGLT2inhibitors include Oaryl inhibitors, C-aryl inhibitors,N-aryl inhibitor, C, Ospiro inhibitors and non-saccharide inhibitors. C-aryl inhibitor has been widely studied for its inability to resist the degradation by β-glycosidase and high activity to lower blood sugar. Dapagliflozin has the highest priority and entered III clinic test. However, the methylene group between the two benzene rings of it can be hydroxylated, which depletes its inhibitory activity. So we design and synthetize a series of gem-dimethyl-bearing C-glycosides as SGLT2inhibitors. These compounds have significant anti-hyperglycemic activities and the substituents at the4-position of the benzene adjacent to the glucose moiety were most preferred.Based on the high activity of this series of compounds, another type of C-glycoside with trans-cyclohexane was designed. These C-glycoside molecules have alkyl group in cyclohexane, such as H, Me, Et, n-Pr,i-Pr, n-Bu, t-Bu, and n-Pentyl group. All of these drugs display strong activities to lower the level of blood sugar in the in vivo activity analysis.Increasing the length of the substituent group elevates its activity, which reaches the peak when the R is Ethanol group, and the activity decreases for the longer substituent group. This is essential to study and fully understand the structure-activity relationship of this type of compounds.The exploration of J’Wang tandem reaction and the synthesis of heterocyclic conjugate molecules are discussed in the third chapter. Compounds containing nitrogen bridgehead heteroaromatic have the characteristic properties in the orbital energy distribution, molecular aggregation and photoelectric performance due to the intramolecular dipole.The fuse-ring conjugate molecules including nitrogen bridgehead heteroaromatic enjoy great potential and vast development prospects. Our team discovered the J’Wang tandem reaction in preliminary work. Another novel tandem reation is found by replacing COOEt with PO(OEt)2, and the PO(OEt)2can be removed in the reaction process. It enriches the organic synthesis methods and promotes the development of the materials. We also explore the N-bridged hetero-pentacyclic compound using J’ Wang tandem reaction.Thiophenodipyrrole is an electron-rich fused-ring group and1,3,4-oxadiazole is an electrophilic group, which are the basis for designing and synthesizing two-photon materials. Thus, we look forward to its prospective application in organic photovoltaic materials.