Studies On Design And Synthesis Of Molecular Tweezers Derived From α-Hyodeoxycholic Acid And Molecular Recognition

The study on molecular recognition using the construction of chemical model or biomimetic system is one of the challenges in the frontiers of bioorganic chemistry. In this dissertation, the efforts were focused on the design and synthesis of molecular tweezers derived from a -hyodeoxycholic acid and their molecular recognition as well as enantioselective recognition. Some useful and important new results have been obtained.Twelve ester-bond molecular tweezers , six aminoacetylate molecular tweezers, four one chiral arm molecular tweezers have been synthesized using a -hyodeoxycholic acid as spacer. All of them are new compounds. The synthetic methods of target compounds have been systemically investigated, and the suitable conditions were chosen. And for the first time, the synthesis of aminoacetylate molecular tweezers was investigated by microwave irradiation, which is simple, effective and friendly to environment. All these tweezer-type receptors possess different sizes of clefts, different rigidity and flexibility, and different chiral centers. Their structures were confirmed by IR, 1HNMR, MS and /or element analysis.Molecular recognition properties of these molecular tweezers for some small neutral molecules, such as some aromatic amines and D/L-amino acid methyl esters were examined by UV-visible spectra titration. The association constant (Ka) and Gibbs free energy changes (- G0) were determined. The computer-aided molecular modeling was used to elucidate further the recognition abilities. The results show that l:linclusion complexes are formed for most of molecular tweezer receptors with guests examined. Some molecular tweezers showed strongrecognition ability for aromatic amines. The association constant can reach 103M-1. Some of these receptors are favorable for complexation with L-amino acid methyl esters. The largest enantioselectivity KL/KD is 11.49. The drive forces of molecular recognition mainly come from non-covalent forces between host and guest, such as H-bond, Stacking interaction etc. At the same time, the rigidity and flexibility of receptors, micro-environmental effects of different cleft structures, the size/ shape-fit and geometry complementary between host and guest also play an important role in recognition process.