Tropine nucleus

The tropine alkaloids are another illustration. Atropine, scopolamine, and cocaine are structurally related, each having the tropine nucleus. While atropine and scopolamine overlap in pharmacodynamic activities, cocaine has uniqueness in this series, being a topical anesthetic and a potent addicting agent. 

The intriguing problem of the mechanism of hydroxylation of the tropine nucleus to give meteloidine (149) remains. The stereochemistry of the hydroxy-groups in (149) precludes an epoxide intermediate like scopolamine, and suggests the involvement of the dioxetan (154). 

These investigations have followed three main lines, (1) alterations in the amino-alcohol nucleus, (2) variation in the alkyl or acyl side-chains, (3) influence of stereoisomerism. Tropine and ecgonine, the basic components of atropine and cocaine, lend themselves to such investigations, but scopine, the amino-alcohol of hyoscine is so labile that systematic modification of this alkaloid has not yet been possible. 

Stereoisomerism in either the alkamine nucleus or the acyl residue has a considerable effect on the pharmacological action of the tropeines and cocaines. Differences in activity of tropine and i/i-tropine and their benzoyl derivatives have been mentioned already, and there seems to be a consensus of opinion that the i/i-cocaines (alkyl- or aryl- acyl esters of 0-ecgonine) are less toxic and more potent local anfesthetics than the corresponding cocaines, derived from 1-ecgonine. ... 

FIGURE 1 8-5 Tissue-specific processing of the pro-opiomelanocortin (POMC) precursor yields a wide array of bioactive peptide products. Processing of the POMC precursor varies in various tissues. In anterior pituitary, adrenocorticotropic hormone (ACTH (1-39)) and P-1 ipo tropin (P-LPH) are the primary products of post-translational processing. Arcuate neurons produce the potent opiate P-endorphin (P-endo (1-31)) as well as ACTIK1 -13) NIT,. Intermediate pituitary produces a-melanocyte-stimulating hormone (aMSH), acetylated P endof 1 31) and P-endo(l-27). NTS, nucleus tractus solitarius. 

Tropane alkaloids have a tropane (C4N skeleton -f) nucleus. Structurally, these alkaloids synthesize as postcursors of pyrrolines (Figure 57). a, /3,

tropane alkaloids (e.g., atropine, hyoscyamine, cocaine, tropinone, tropine, littorine and cuscohy-grine) have a strong biological activity, especially as neurotransmitters. 

Tropane is formed when pyrrolidine and piperidine are condensed. Closely related to tropane are tropine, the principal nucleus of the solanaceous alkaloids, atropine, hyoscyamine, hyoscine, and belladonnine, and ecgonine, the nucleus of cocaine (Figure 11.7). 

Plants in the Solanaceae family produce a variety of alkaloids, some of them having a considerable therapeutic importance. One such group of alkaloids possesses a tropane nucleus. Tropane alkaloids are structurally related natural products having in common the azabicyclo[3.2.1]octane structure and therefore the systematic name for tropane is 8-methyl-8 azabicyclo[3.2.1]octane (Fig. 1). The majority of these alkaloids are esters between organic acids and hydroxytropanes. 3a-Hydroxytropane, called tropine, is the amino alcohol most frequently encountered. In addition, its 3 (3-isomer (pseudotropine), the di- (3,6- 3,7- or 6,7-) and trihydroxylated... 

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). 

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