The Pyridine Alkaloids

Nearly all of the microbial and mammalian transformation studies with this group of alkaloids have been focused on nicotine. Microorganisms have been used to resolve racemic nicotine to make available unnatural (/ )-(+)-nicotine for biological evaluation. Highly significant work has detailed the mechanism of nicotine oxidation in mammals, and has resulted in the identification of reactive intermediates formed as the alkaloid is transformed by hepatic monooxygenases. The chemistry and pharmacology of the pyridine alkaloids is discussed by Strunz and Findlay in Volume 26 of this treatise. 

The pyridine alkaloids anabasine (1), nicotine (2), ricinine (3), nomicotine (4) and trigonelline (5) form an important group of natural products. Thus anabasine (1) is extracted on a large scale in the Soviet Union (56MI20900) and functions as an insecticide with acute and subacute toxicity. Nicotine (2) has been used as an anthelmintic but more widely as an agricultural insecticide, functioning as a contact poison when combined with oleic acid... 

The thiol group can also be found in heterocyclic compounds such as 2-mercaptobenzothiazole (9) and echinoclathrine C (10). Compound 9 was isolated from the symbiont bacterium Micrococcus sp., which was obtained from the sponge Tedania ignis [13]. The pyridine alkaloid echinoclathrine C (10) and its S-acetylated derivative, echinoclathrine B (11), were isolated from the Okinawan sponge Echinoclathria sp. [14]. The position of the hydroxyl and acylamino group on the phenyl ring in echinoclathrines (11 and 10) was recently corrected [15]. Compound 11 showed weak immunosuppressive activity in the mixed lymphocyte reaction assay with an IC50 of 9.7 pg/ml [14]. 

Kava contains the pyridine alkaloid pipermethystine, the chalcone flavokavain, the norsesquiterpenoid dihy-drokavain, and the pyran tetrahydroyangonin. 

Alkaloids are classified according to their heterocyclic rings. For example, cocaine, a central nervous system stimulant, and atropine, a muscle relaxant, are examples of the tropane alkaloids in which a nitrogen appears in a bridge of a seven-membered ring structure. Nicotine, the addictive and toxic component of tobacco, is an example of the pyridine alkaloids in which a nitrogen appears as a member of a six atom aromatic ring. (Nicotine is an effective insecticide.) The addictive... 

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