Synthesis And Application Of Pyrrole Indoline Derivatives

Pyrrolidino[2,3-b]indoline framework derivatives,with the unusual heterocyclic core skeleton and varied biological activities,consist in plants or secondary metatolites of microorganisms.The synthetic challenge was posed by the unique molecular structures replete with sterically congested stereogenic centers.This paper interested in exploiting some novel efficient synthetic methodologies to access 3a,3a′-bispyrrolidinoindoline and C3a alkoxylated monomeric pyrrolidinoindoline,and directly applied to the concise synthesis of pyrrole[2,3-b]indoline type natural products.Our study including the following aspects:The first part focuses on the one-step catalytic synthesis of 3a,3a′-bispyrrolidinoindoline.The easily available N-Me tryptamine was originally chosen as model substrate to systematic optimizing the catalytic conditions,such as coordination anion,ligand,solvent,etc.Finally,we have successfully developed the cooperative dual copper-catalyzed tandem cyclization and dimerization of tryptamine under mild air oxidation conditions,affording the amine substituted 3a,3a′-bispyrrolidinoindolines in good yields with high levels of chemical selectivities.This protocol is practical and synthetically useful,by employing this protocol,the highly step-economical divergent total synthesis of bio-active natural products（±）-folicanthine and meso-folicanthine were accomplished.The second part focuses on the one-step catalytic synthesis of C3a alkoxylated monomeric pyrrolidinoindoline.we started our studies with Cu Br₂ as metal catalyst.Finally,we have developed copper-catalyzed alkoxycyclization of tryptamine under mild O₂ oxidation conditions,affording C3a-alkoxylation pyrrolidinoindolines in good yields with high diastereoselectivities.this protocol was proved practicable and useful by the rapid concise total synthesis of natural product CPC-1.The third part focuses on biological evaluation tests on the above-mentioned natural products and partial their derivatives.According to unreported potential activities,the growth inhibition assay operated in HEL,K562,A549,LNcap tumor cell lines in vitro.The result indicated that these compounds were negative in inhibit the growth of HEL,K562,A549,LNcap tumor cells.