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.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000470:Alkaloids / Q000032:analysis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003078:Colchicine / Q000138:chemical synthesis; D008968:Molecular Conformation; D011725:Pyridines / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000470:Alkaloids; D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003078:Colchicine