Design,Synthesis And Biological Activity Of Cannabidiol And Cyclodextrin Conjugate And Per-Amino-Cyclodextrin Catalyzed Asymmetric Reaction In Water

Cyclodextrin has been widely used in the fields of drug carriers and supramolecular catalysis due to its molecular recognition,easy derivatization,economic and environmental protection,and biological safety.In the field of drug carriers,cyclodextrin,as a natural oligosaccharide molecule,has good water solubility,and its hydroxyl group is easily derived and covalently combined with poorly soluble drugs to form a drug-cyclodextrin conjugate to improve the water solubility and stability of the drug and bioavailability.In the field of supramolecular catalysis,cyclodextrin is used in aqueous phase catalysis in a form similar to natural enzymes.The cavity can contain hydrophobic substrates to form specific host-guest inclusion compounds,fix the steric position of the substrate and use hydroxyl or derivative groups as reaction catalyst sites to catalyze the reaction.Therefore,the design and development of cyclodextrin-based drug carriers and supramolecular catalysts have high research value.Cannabidiol has anti-epileptic,anti-convulsant,anti-cancer,analgesic,immune regulation,whitening and other pharmacological effects.However,its poor water solubility and stability greatly limit the clinical application of cannabidiol.Therefore,we designed a cannabidiol-cyclodextrin conjugate to overcome these shortcomings.Supramolecular catalysis is a form closest to natural enzyme catalysis,and it is also a novel way of catalysis.The amphiphilic characteristics of cyclodextrin and its derivatives,which are hydrophilic on the outside and hydrophobic on the inside,determine its application in aqueous phase reactions,and can effectively avoid the use of toxic organic reagents and expensive reagents.However,in the existing reports,the reports of cyclodextrin-catalyzed stereoselective reactions are very rare,so there is a lot of room for development and challenges.The research content consists of the following two parts:1.The β-cyclodextrin was derivatized with a single amino group to obtain 4 types of monoamino-substituted cyclodextrins with different chain lengths.The phenolic hydroxyl group of cannabidiol is derivatized with carboxylic acid to obtain a cannabidiol carboxylic acid derivative with a carboxyl functional group.Then,4 kinds of monoamino-substituted β-cyclodextrins with different chain lengths and cannabidiol carboxylic acid derivatives were covalently combined into 4 kinds of cannabidiol-cyclodextrin conjugates by amide condensation reaction.The successful preparation of the coupling compound was proved by ¹H NMR,¹³C NMR,HR-MS and IR.Through TGA,UV-Vis and saturated solution methods,it was proved that the thermal stability,light stability and water solubility of the four coupling compounds were significantly higher than that of cannabidiol.Finally,the MTT experiment confirmed that the conjugate has certain toxicity to Hela,MCF-7 and HepG2 cell lines.2.Using β-cyclodextrin as a raw material,a three-step reaction is used to prepare per（6-amino）- β-cyclodextrin.Study it as a catalyst to catalyze asymmetric Mannich reaction and asymmetric Aldol reaction in the water phase.The structure of the reaction product was characterized by ¹H NMR,¹³C NMR and HR-MS.HPLC determines the enantiomeric excess value of the product.The result shows:（1）The asymmetric Mannich reaction achieved high stereoselectivity（92%ee value）,but the yield was low（5%）;（2）An ee value of 98%was obtained in the asymmetric Aldol reaction with acetone and p-nitrobenzaldehyde as the substrate.