THE ENANTIOSPECIFIC SYNTHESIS OF (-)-MONOMORINE FROM L-GLUTAMIC ESTER

Diethyl L-glutamate hydrochloride (3) was converted to its N-pyrrole derivative 5. Submission of 5 to butyryl chloride in boiling toluene gave the 2-butyryl derivative, and by treatment with NaBH3CN and ZnI2, the 2-butyl analogue 9. Cyclization of 9 with BBr3 afforded (5S)-3-butyl-5-ethoxycarbonyl-5,6-dihydro-8(7H)-indolizinone (10). Hydrogenation of 10 over Pd/C in acidified EtOH gave (3S,5S,9R)-3-butyl-5-ethoxycarbonylindolizidine. By successive reduction of the latter to the primary alcohol, formation of the chloride and reductive dechlorination with tributyltin hydride, (3S,5R,9R)-3-butyl-5-methylindolizidine, or (-)-monomorine, was obtained in 8 steps from 3 in a yield of 25%.