Further explorations of unnatural alkaloids

(+/-)-N1-noreseroline-O-methyl-ether, prepared by a modification of the Julian total synthesis, afforded with R-(+)-methylbenzyl-isocyanate two diasteromeric ureas, converted individually into (+)- and (-)-eseroline after thermolysis, N-methylation and O-demethylation. (+)-Physostigmine was obtained after reaction of (+)-eseroline with methylisocyanate. Biological properties of (-)- and (+)-eseroline and (+)-physostigmine will be reported. (+/-)-Colchicine, prepared from the natural alkaloid by a Bladé-Font procedure was converted into a variety of racemic colchicinoids. Chemical resolution of (+/-)-deacetylcolchicine and (+/-)-deacetylisocolchicine afforded the desired pairs of optical isomers. Discussion on structure-activity-relationship of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) will include phenyl-substituted isomers, N-alkyl analogs, an "open-ring"-isomer, as well as pyridones, obtained by oxidation of quaternary pyridinium and dihydropyridinium species. A diagram of MPTP X HCl, obtained by solid state X-ray diffraction analysis will be shown.