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.