| The research and development of silicon substitution of new drugs refers to the structure of existing drugs for silicon modified to get biological activity drugs.Compared with carbon,silicon lipotropy,electronegativity,atomic size and covalent radius are different.These differences make silicon substitution of new drugs show superior properties:1,The silicon substitution agent contains silanol functional groups.Compared with the methanol functional groups,the hydrogen bond energy of silicon alcohol functional groupsis more big,which strengthen the affinity between drug and the receptor and improve the selectivity of drugs.2,Silicon substitution of drugs has higher lipotropy and has very strong tissue penetration ability to obviously increase the distribution volume of drugs.What,s more.they can improve the apparent oil-water partition coefficient and improve the permeability of blood brain barrier drugs.which significantly improve the therapeutic efficacy of drugs.3,The drug toxicity of silicon-containing drugs is low and the safety of drugs is improved.The synthesis research of silicon-containing drugs attracts more and more people’s attention.How effective and convenient to synthetic silicon compounds have become an urgent problem.We are interested in the 1.2-addition of nucleophilic silicon to aldehydes.Because their products posess α-hydroxyl silicon which have been widely used in the construction of C-Cand rearrangement.We connected planar chiral[2.2]paracyclophane with N-heterocyclic carbene to get a kind of novel ligands and they were successfully applied to the addition of nucleophilic silicon to aldehydes,which generates a series of α-hydroxy silicone products.This paper includes the following several aspects:Chapter 1,The research background.The research and development of silicon substitution of new drugs,asymmetric silicon addition reaction,the application of NHC in asymmetric catalytic reactions and the application of[2.2]paracyclophane in asymmetric catalytic reactions were reviewed.Chapter 2,Thedesign and synthesis of triazolium salts based on planar chiral[2.2]paracyclophane and their structural characterization.The synthesis of target ligands need to first prepare two raw materials.They are respectively formyl hydrazine salt and chiral imine ether.On the one hand,we used dimethyl benzyl trimethyl ammonium chloride as starting materials.The[2.2]paracyclophane was achieved by Hofmanm eliminate and free radical polymerization.Then by bromination,the high temperature inversion and amination,4-amine-12-bromo[2.2]paracyclophane was obtained.The Rp/Sp optically pure products were gotten by column chromatography separation.Soon afterwards we got the formyl hydrazine salts by diazotization,bromination amination,single hydrazone,formylation and Suzuik reaction.On the other hand,we took the L-benzene ammonia alcohol as raw materials,after amidation,amunation and methylation,the chiral imine ether was obtained.Finally formyl hydrazine salt reacted with chiral imine ether to yield triazolium salts based on planar chiral[2.2]paracyclophane.Chapter 3,Metal-free catalytic enantioselective addition of nucleophilic silicon to aldehydes by[2.2]Paracyclophane-Based N-Heterocyclic carbene catalystWe used4-chlorobenzaldehyde as templatesubstrate.The optimal reaction conditions was developed by the optimized conditions and ligand screening.Then we developed metal-free catalytic enantioselective addition of nucleophilic silicon to aldehydes by[2.2]Paracyclophane-based N-heterocyclic carbene catalyst.A series of a-hydroxy silicone products were obtained.The innovation of this paper:1,We firstsuccessfully synthesized the[2.2]Paracyclophane-based N-heterocyclic carbene catalystmodified by phenol.2,We first developed metal-free catalytic enantioselective addition of nucleophilic silicon to aldehydes by[2.2]Paracyclophane-based N-heterocyclic carbene catalyst. |
