The Study On [3+2] Cycloaddition To Construct The Total Synthesis Of Spirotryprostatin And Elacomine Alkaloids

The pyrrole ring skeleton exists widely in the structure of drugs and natural products.Therefore,pyrrolidine derivatives are widely used in the synthesis of numerous drugs and natural products.Moreover,asymmetric synthesis of pyrrolidine derivatives has become a hot topic in organic synthesis feild.[3+2]cycloaddition reaction between azomethimine ylide and electron-deficient multiple bonding compounds,which is the most convenient and efficient method to construct the pyrrole ring skeleton.Accordingly,the following studies have been carried out in the thesis:1.Studying on[3+2]cycloaddition reactions:Firstly,32 endo-pyrrolidine derivatives（up to 98%yield,98:2 dr）were synthesized by using Ag₂O（2 mol%）/PPh₃（4 mol%）/TEA（20 mol%）as a catalyst for the[3+2]cycloaddition reaction betweenα-substituted ethyl acrylate and azomethimide ylide.Then,using Ag₂O（2 mol%）/PPh₃（4 mol%）/TEA（20 mol%）as a catalyst,17 exo-pyrrolidine derivatives（up to 80%yield,88:12 dr）were synthesized by the[3+2]cycloaddition reaction betweenα-substituted tert-butyl acrylate and azomethimide ylide with large resistance.Finally,36 chiral exo-pyrrolidine derivatives were synthesized by using Ag HMDS（5 mol%）and the chiral diphosphine ligand S-DTBM-Segphos（5 mol%）as a catalyst for the asymmetric[3+2]cycloaddition reaction.This catalyst promoted the high yield（up to 98%）,high enantio-and diastereo-selectivity（up to>99%ee,>99:1 dr）in the reaction betweenα-substituted tert-butyl acrylate and azomethimide ylide.These methods provide good theoretical possibilities for the subsequent synthesis of alkaloids（±）-Elacomine and Spirotryprostatin A.2.Studying on the form synthesis of alkaloid（±）-Elacomine:Based on the above experiment,isoamylaldehyde-derived azomethimine ylide and 2-（2-nitro-4-methoxyphenyl）-ethyl-acrylate were utilized as reacants.After 8 steps as[3+2]cycloaddition,protection,decarboxylation,deprotection,etc.,the important precursor compound of target natural product（±）-Elacomine was synthesized successfully in 36%overall yield.3.Studying on the asymmetric synthesis of alkaloid Spirotryprostatin A:employing 2-butynaldehyde-derived azomethimine ylide and 2-（2-nitro-4-methoxyphenyl）-tert-butyl-acrylate,the alkaloid Spirotryprostatin A in 23%overall yield via 11 steps was synthesized successfully,such as asymmetric[3+2]cycloaddition,acylation,condensation,etc.