Studies On Stereo-Structures For Organic Compounds And Establishing Of Analytical Method For Medicinal Polymorphism By X-Ray Diffraction

X-ray diffraction is a fast and efficient physical method for the study of molecular structure and the component (phase) of a compound. With X-ray diffraction analysis, we can determine the structures of natural products and synthetic compounds, study on the drug polymorphism and provide accurate data of stereo-structures for computer-aided drug design. X-ray diffraction analysis consists of two techniques: single crystal X-ray diffraction and powder X-ray diffraction. Using the two techniques and combined with modern isolation methods and other analytical approaches, the determination of stereo-structures of a number of compounds, the studies on the medicinal polymorphism and related researches of some higher fungi were accomplished in this thesis.Using single crystal X-ray diffraction, we can solve many problems for the chemists and provide them with the stereo-structure information, such as bond lengths and angles, torsion angles, dihedral angles, configuration, conformation, hydrogen and salt or coordination bonds, the type and amount of solvents in the molecule. The accurate structures are basic data for computer-aided drug design. To obtain high quality single crystals is a precondition and basis for single crystal X-ray diffraction analysis. Sixty-nine suitable single crystals which were difficultly obtained have been cultivated by solvent growth method and seeding crystal method. With direct method and Patterson method, a total of 90 compounds were analyzed and their three-dimensional structures were obtained, including many completely unknown, difficult to analyze and new molecular skeleton compounds. Those structures cover coumarins, terpenes, steroids, alkaloids and cyclopeptides, etc., which provided a lot of basic data for drug research and development.Using single crystal and powder X-ray diffraction analytical techniques, the polymorphisms of seven medicines were studied including Thalidomide, Lamivrdine, Adefovir dipivoxil, Riluzole, PHPB, CHU-9126 and XLF-343. Through a series of experiments, the molecular structures of 16 polymorphism samples were gained and the rules of the molecular arrangement in different polymorphism were disclosed. Standard powder diffraction patterns of all the 16 polymorphisms were established. In addition, the systematic study on the polymorphisms of XLF-343, which is an innovative and solid drug, indicated that at least 5 polymorphisms were obtained, including 4 crystalloids and 1 amorphism. The pharmacological experiments showed that the bioavailability of the amorphism is the highest. The experiments of the polymorphism exchange were completed and the most optimum conditions to get amorphism were obtained. The quantitative analysis of the polymorphism and the calibration curve were achieved and the standards for the quality control were set up.In the last part of the thesis, the proteins of 5 special higher fungi in Yunnan Province have been studied including Russula virescens Fr. , Lactarius hatsudake Tanaka, Psathyrella Camdolleana, Pholiota mutabilis, Ganoderma sessile Murr. After the extraction and separation of those proteins, 40 fractions were obtained. And qualitative analysis, SDS-PAGE analysis and powder X-ray diffraction were carried out on the fractions. In a high-throughput screening (HTS), including anti-tumor model, anti-fungi model,β-Setetase inhibitor model, anti-oxidation model, 2 fractions were found to display high bioactivities. It laid a foundation for future research to understand their bioactivities and to search for potential lead candidates from higher fungi.