Study On The Synthesis Of New PDI Inhibitors And P53-MDM2 Inhibitors And The Inclusion Behavior Of Acetyl Gastrodin/cyclodextrin

The compounds containing the chalcones nucleus structure usually have important biological activities,including anti-fungal,anti-viral,anti-tumor,and anti-malarial activities.At present,some drugs containing chalcone skeletons are already on the market or in clinical trials.The spirofluorene compounds are widely found in drug molecules and natural products.They are often used as effective pharmacophores in the design of new drugs.Therefore,the development of new methods for synthesizing chalcone compounds and spirocyclines is of great significance for the development of new drugs.Acetyl gastrodin has the effect of calming and sleeping and can balance the excitement and inhibition of the cerebral cortex.Acetyl gastrodin tablets are drugs that have been reviewed by the State Food and Drug Administration and have a good therapeutic effect on migraine.Due to poor water solubility of acetylated gastrodin,poor absorption in the gastrointestinal tract limited the promotion of acetylated gastrodin in the clinic.Cyclodextrins,as a commonly used pharmaceutical excipient,will improve the physicochemical properties of drugs and increase their bioavailability.This paper mainly carried out the following three aspects of the research work:Chapter 1: Acetylbenzenesulfonyl chloride and polycyclic imines are reacted under conditions of tetrahydrofuran and DIPEA to form p-acetylbenzenesulfonamide compounds,followed by meta-substituted benzaldehyde under the condition of CBr4 as catalyst.In a solvent-free reaction,26 chalcone compounds were synthesized with a yield of 78%-94%.And some of these compounds were screened for in vitro anti-tumor activity screening experiments.Chapter 2: This chapter starts with a three-pot one-pot method to synthesize a series of novel 3-quaternarycarbon-spirooxindole based on the structures of isatin,L-Proline and 4,4-dimethoxycyclopentadienone.Among them,19 compounds were synthesized by solvent-free method,and 7 compounds were synthesized using methanol as solvents.The utilization rate of the reaction was high,and the green color was clean,which greatly expanded the compound library of these compounds.And some of these compounds were screened for in vitro anti-tumor activity screening experiments.Chapter 3: In this chapter,three cyclodextrin inclusion complexes of acetylated-gastrodin/β-cyclodextrin,acetylated-gastrodin/γ-cyclodextrin,andacetylated-gastrodin/H P-β-cyclodextrin were prepared.The inclusion complexes were identified by nuclear magnetic resonance,infrared,ultraviolet,X-ray powder diffraction,thermal analysis,and scanning electron microscopy.The formation and characterization of it.The results will provide a theoretical basis for the study of new formulations of acetylated gastrodin.