Short,Enantiospecific Syntheses of Indolizidines 209B and 209D,and Piclavine A from Diethyl-L-Glutamate

The 1H-pyrrole derivative obtained from diethyl L -glutamate hydrochloride and tetrahydro-2,5-dimethoxyfuran was cyclized with BBr₃ to ethyl (5S)-5,6,7,8-tetrahydro-8-oxoindolizine-5-carboxylate ( 18 ). Catalytic hydrogenation of 18 over Pd/C in AcOH gave ethyl (5S,8aR)-octahydroindolizine-5-carboxylate ( 21 ), whereas hydrogenation over Rh/Al₂O₃ in EtOH/AcOH 99:1 afforded mainly ethyl (5S,8S,8aS)-octahydro-8-hydroxyindolizine-5-carboxylate ( 22 ). By functional-group interconversions, 21 was transformed into piclavine A ( 1 ) and indolizidine 209D ( 2 ). Similarly, (5R,8R,8aS)-octahydro-5-pentylindolizine-8-methanol ( 37 ), the final relay for indolizidine 209B ( 3 ), was obtained from 22 .