SYNTHESIS OF (-)- AND (+)-ESERMETHOLE VIA CHEMICAL RESOLUTION OF 1,3-DIMETHYL-3-(2-AMINOETHYL)-5-METHOXYOXINDOLE

Article abstract of DOI:10.1016/S0957-4166(00)80490-5

A new synthesis of (-)- and (+)-esermethole (2 and 7 respectively), penultimate intermediates to (-)- and (+)-physostigmine, is described.Phase-transfer catalyzed dimethylation of 3-cyanomethyl-5-methoxyoxindole (3) and successive hydrogenation of the cyano group gave 1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole (5), which was efficiently resolved with optically active tartaric acids.Subsequent conversion to a carbamate and reductive cyclization performed by a standard method afforded both the enentiomers of esermethole.The enantiomeric excesses, determined by chiral HPLC analysis, were greater than 99.5percent.In particular, analitycal HPLC resolution of 5, previously reported as unfeasible, was achieved.