Asymmetric Synthesis Of Indoline Derivatives And Their Applications In The Synthesis Of Natural Product(-)-Angustureine

As a characteristic structural motif of numerous natural products and biologically active new drugs, chiral indoline derivatives have attracted much attention of human being. The potential pharmacological and physiological activity of the natural product(-)-angustureine as antibacterial and for the treatment of spinal and neurological disorders also attracted the interests of researchers. Although many scientists has made lots of efforts for its synthesis, to explore a new, simple and efficient asymmetric synthetic methodologs still had a great value in the field of biochemistry and medicine.Using(1S,2R)-(+)-2-amino-1,2-diphenylethanol as the starting material, the Williams intermediate was obtained in a high yield according to the literature. Starting from the Williams intermediate,(R)-indoline-2-carboxylate was obtained with high selectivity through nucleophilic substitution, deprotection, protection and intramolecular coupling reaction.Through modification of the benzene ring, a variety of(R)-indoline-2-carboxylate derivatives were synthesized.Using the(R)-indoline-2-carboxylate as the starting material, after reduction, Grignard reaction, removal of the protecting group on the N atom, expansion of the five-membered ring to the desired six-membered skeleton, dehalogenation and N-methylation, we finally got the natural product(-)-angustureine.