Tropane chemistry is a division of chemistry where tropane alkaloids and synthetic tropeines are discussed. Man has been using tropane alkaloids since prehistoric times, but collection of their chemical data was achieved recently in last two centuries. Now days, with the evolution of data, a separate division for tropane alkaloids and tropeines may be suggested for understanding .
Tropane is a bicyclic amine, characterized by a two-ringed structure with a pyrrolidine and a piperidine ring sharing a single nitrogen atom and two carbon atoms. Thus, the common structural element of the tropane alkaloids is the bicyclic azabicyclo-octane skeleton (Lounasmaa and Tamminen, 1993).
Fig: Tropane structure (all equivalent)
Tropane alkaloids have been found in different plant families, Brassicaceae (Cruciferae), Convolvulaceae, Erythroxylaceae, Euphorbiaceae, Olacaceae, Proteaceae, and Rhizophoraceae, but they are best known for their occurrence in the family Solanaceae (Griffin and Lin, 2000). The family Solanaceae comprises about 100 genera and 3000 species. Particularly the genera Datura, Brugmansia, Hyoscyamus, Atropa, Scopolia, Anisodus, Przewalskia, Atropanthe, Physochlaina, Mandragora, Anthotroche, Cyphantera, and Duboisia are known as being rich in tropane alkaloids (Griffin and Lin, 2000).
Chemistry of tropane alkaloids:
The wide range of tropane alkaloids occurring in the Solanaceae family arises from the esterification of acids, such as acetic acid, propanoic acid, isobutyric acid, isovaleric acid, 2-methylbutyric acid, tiglic acid, α-hydroxy-β-phenylpropionic acid, tropic acid, and atropic acid with various hydroxytropanes (α-tropanol, α− tropane-diol or α-tropane-triol). Tropane alkaloids from Erythroxylaceae family contains benzoic acid.
While Erythroxylaceae family produces esters of benzoic acid, cinnamic acid; 3,4,5-trimethoxybenzoic and 3,4,5-trimethoxycinnamic acid residues with 2-carbomethoxytropane-3α-ol; 6,7- dihydroxytropane-3α-ol; or 6- hydroxytropane-3α-ol.
Fig: Various types of carboxylic acids found in tropane alkaloids
The most important natural tropane alkaloids, hyoscyamine, scopolamine, and cocaine are esters of tropane-3α-ol, 6,7-epoxytropane-3α-ol, 2-carbomethoxytropane-3α-ol and tropic acid.
Fig. Some natural tropane alkaloids
(Cordell, 1981; Leete, 1989; Robins and Walton, 1993; Humphrey and O’Hagan, 2001)
Tropane alkaloids like other alkaloids are usually found in the seeds, root, leaves, or bark of the plant. A common method of isolation of these alkaloids is as follows. The plant is dried, then finely powdered and extracted with boiling methanol. The solvent is distilled off, and the residue is treated with inorganic acids, whereupon the bases are extracted as their soluble salts. The free bases are liberated by the addition of sodium carbonate and extracted with various solvents, e.g., ether, chloroform, etc. The mixtures of bases thus obtained are separated by various methods into individual compounds. Most recent methods of separation involve the use of chromatography. Now days most Tropane analogs are synthesized but alkaloids like atropine, hyoscyamine and scopolamine are still obtained from natural sources.