Chiral Bisoxazoline Copper (?) Catalyzed Asymmetric Synthesis Of MacrocyclicDouble Lactones And Lactams With Pyrrolo-Indolyl Backbones

Macrocyclic compounds with nitrogen-containing heterocyclic skeletons are important structures of many natural products and drug molecules.Moreover,these compounds have quite extensive application in medicine,pesticide,dye as well as other fields.Although the synthesis of various macrocyclic compounds has been reported,their efficient and asymmetric synthesis is still challenging.In this thesis,with the strategy of asymmetric tandem reactions catalyzed by chiral ligand-metal complexes,a series of ?,?-unsaturated ?-keto acid tryptophol esters and ketoamide compounds were designed and synthesized.Furthermore,the asymmetric synthesis of enantiomerically enriched macrocyclic double lactones and lactams with pyrrolo-indolyl backbones were realized.The reaction provides a new approach for the asymmetric synthesis of macrocyclic compounds containing nitrogen-containing heterocyclic skeleton.In my first part,by the use of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride(EDCI)and 1-hydroxybenzotriazole(HOBt)as condensation reagents,condensation esterification and carboxylic acid-amine condensation reactions were smoothly carried out between various substituted tryptophols or tryptamines and ?,?-unsaturated ?-keto acids.A series of ?,?-unsaturated ?-keto acid tryptophol esters and ketoamide derivatives were effectively constructed in moderate to good yields.The structures of the two types of compounds were characterized by NMR,HRMS and IR spectroscopic spectra.The reported synthetic method has the advantages of readily available raw materials,mild reaction conditions and convenient manipulation.In my second part,the intermolecular cascade reactions well proceeded between two molecules of ?,?-unsaturated ?-keto tryptophol esters or ketoamides in the presence of chiral Box/Cu(?)complexes as the catalysts.In addition,the hydroxyl groups of the reaction intermediates were protected with acetic anhydrides.According to the literatures reported and control experiments,the double Friedel-Crafts alkylation/N-hemiketalization cascade process was proposed.The desired macrocyclic double lactones and lactams with pyrrolo-indolyl backbones were obtained in high yields with excellent enantio-and diastereoselectivity.