Further Explorations of Unnatural Alkaloids

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Abstract
(.+-.)-N1-noreseroline-0-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 methyl-isocyanate. Biological properties of (-)- and (+)-eseroline and (+)-physostigmine will be reported. (.+-.)-Colchicine, prepared from the natural alkaloid by a Blade-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 .cntdot. HCl, obtained by solid state X-ray diffraction analysis will be shown.