Scopolic acid

The bromine-free hydroscopoline (like dihydroxytropane) is readily oxidized by chromic acid to scopolic acid or l-methylpiperidine-2,6-dicarboxylic acid (65, 68) which has since been synthesized (65, 161, 163). The oxidation of the dihydroxy compound, hydroscopoline, to a hydroxyl-free piperidine derivative would suggest (1) that there is a piperidine nucleus (also that pyridine is formed by the zinc dust distillation of norscopoline (64)) in hydroscopoline (and hence in scopoline) and (2) that the hydroxyls of hydroscopoline are not attached to the piperidine nucleus of this base. The close relationship of scopoline to tropine was first established by the reduction (hydriodic acid and phosphonium iodide at 200°) of hydroscopoline to tropane (167). Dihydroscopoline must be a dihydroxytropane with the hydroxyls, of necessity, located in the pyrrolidine nucleus to account for its oxidation to scopolic acid (LXI —> LXII). 

Failure to isolate a halogenated scopolic acid from the oxidation of hydroscopoline chloride has prompted some workers to conclude that the chlorine of hydroscopoline chloride, and hence the ether bridge of scopoline, cannot be attached to C2, C3, or C4 (170). This, combined Avith exhaustive methylation studies, favored a Cs-C ether bridge (LXIIIB). 

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