Strychnine and related alkaloids

Corymine, strychnine, and related indole alkaloids (AA) Histrionicotoxin and related piperidines (AA) ibogaine and related indole alkaloids (AA) nudferine and related aporphine alkaloids (AA)... 

Serotonin is metabolized to bufotenin, and much of this is excreted in the urine as a glucuronide conjugate [56]. Vindoline and related alkaloids of Catharanthus roseus are extensively metabolized by mammals through the actions of esterases, peroxidases, and P-450 oxidases [57]. Oxidation of vindoline and vinblastine occurs in human serum, catalyzed by ceruloplasmin [58], The major metabolite of yohimbine is 11-hydroxyyohimbine, but the 10-hydroxy derivative is also produced [59], Strychnine injected into rats gives as its major metabolite its 21,22-epoxide, but other epoxidized and hydroxy derivatives are also prodced [60]. Harman is hydroxylated at C-6 by mice [61]. 

Leuchs initial elan, fed by intelligence and power of imagination, which after successful (albeit by Emil Fischer inspired) peptide studies launched him into the difficult chemistry of strychnine alkaloids and also into problems of stereochemistry, diminished later, probably under the influence of some decisive inner experience unknown to us. After a while his life was consumed by work in the laboratory he remained unimpressed by the rich cultural and scientific distractions offered by Berlin, that time in its heydays. After 1908 his principal field became strychnine chemistry and related alkaloids 125 of his 178 publications deal with this topic. 

Schematic biogenesis of Strychnine-type and related alkaloids...

Nicotine boldine and other aporphine alkaloids C-toxiferine coniine and other piperidine alkaloids cytisine and other quinohzidine alkaloids epibatidine tubocurarine Berbamine, berberine, and other isoquinoline alkaloids cinchonidine and other quinoline alkaloids corynanthine, yohimbine, and other indole alkaloids emetine ephedrine ergometiine and related ergot alkaloids Ergocornine and related ergot alkaloids bulbocapnine and related aporphine alkaloids anisocycline, stylopine, and related protoberberine alkaloids salsolinol and related isoquinohnes BicuculUne, cryptopine, hydrastine, and related isoquinoline alkaloids securinine harmaline and related beta-carboline alkaloids Corymine, strychnine, and related indole alkaloids Histrionicotoxin and related piperidines ibogaine and related indole alkaloids nuciferine and related aporphine alkaloids... 

Optica] resolution of these and related carboxylic acids were achieved using salt formation with alkaloids (strychnine, brucine, cinchonidine) 33,39,44 or with optically active amines [1-phenyl- or l-( 3-naphthyl)ethylamine]4o,44). The following rotations [a]D have been reported [8]paracyclophanecarboxylic acid (13) +18° (chloroform)441 [10]homologue (14) +80° (chloroform)39 and +67° (chloroform)40 its methyl-derivative (75) —28° (methanol)44 . Dioxa[10]paracyclophanecarboxylic acid (16) + 104° (ethanol)36 and bromo-dioxa[12]paracyclophanecarboxylic acid (79) —37° (acetone)33). 

Aconitine and related diterpene alkaloids (A) veratridine, zygadenine, and related steroidal alkaloids (A) ajmaline, vincamine, ervatamine, and other indole alkaloids (AA) dicentrine and other aporphine alkaloids (AA) gonyautoxin (AA) paspalitrem and related indoles (AA) phalloidin (AA) quinidine and related quinoline alkaloids (AA) sparteine and related quinolizidine alkaloids (AA) saxitoxin (AA) strychnine (AA) tetrodotoxin (AA)... 

Francois Magendie, 1783-1855 born in France, researched the different motor functions of the body in relation to the spine, as well as nerves within it. In addition, he researched the effects of morphine, quinine, strychnine, and a multitude of alkaloids. Noted as the father of experimental pharmacology. 

MacMillan has recently described concise and enantioselective S3mtheses of strychnine and several related alkaloids (S. B. Jones, B. Simmons, A. Mastracchio and D. W. C. MacMillan, Nature, 2011, 475, 183) ... 

From 26 they could access a series of structurally related alkaloids from the Strychnos (Strychnine), Aspidosperma, and Kopsia families and from 27 Minliesine was accessible, which is structurally different alkaloid from the Strychnos family. 

Although the related alkaloid brucine (and possibly also vomicine [867, 868]) would appear to exhibit activity which is qualitatively identical [869] but quantitatively less potent [870], strychnine (LIII, Fig. 4) [871] can be regarded as a structurally specific drug on account of its specific action on the post-synaptic inhibitory mechanisms in the spinal cord [754, 872-881]. Indeed, so specific is this activity that the recent demonstrations [882-885] that strychnine appears to block only some of the post-synaptic inhibitory mechanisms in the cerebral cortex are open to the interpretation [882, 886-890] that the mechanisms unaffected by the drug in this location utilise a different transmitter from the transmitter involved in the spinal cord. 

The securinega alkaloids occur in several species of the Securinega and Phyllan-thus genera (150). Securinine was first isolated from the leaves and stems of Securinega suffruticosa (Euphorbiaceae). Securinine nitrate is a central nervous system stimulant similar to strychnine but less toxic. It was found to be useful in treatment of paresis and paralysis following infectious diseases and psychic disorders. The related alkaloids were obtained from Securinega suffruticosa allose-curinine, dihydrosecurinine, securinol A, and securinol B from the leaves, and securitinine from the roots. 

Fused carbazoles related to pyrido[4,3-6]carbazole alkaloids were prepared by a Diels-Alder route, and a 3-aza bioisostere of the antitumor alkaloid olivacine was synthesized <02CPB1479>. Indoloid [3.3]cyclophane 40a gave the pentacyclic indoloid 41a upon heating <02OL127>. This led to a concise formal total synthesis of ( )-strychnine in 12 facile steps from tryptamine when a similar transannular inverse-electron-demand Diels-Alder reaction of indoloid [3.3]cyclophane 40b gave 41b <02AG(E)3261>. 

Alkaloids are widespread in plants and include some very well-known poisons (notably coniine and strychnine), hallucinogens (morphine, cocaine and muscimol) and other potentially lethal compounds that are nevertheless used in medical practice (e.g. atropine, codeine, colchicine and morphine). As indicated by the preliminary snap-shot above, alkaloids typically have names ending in -ine and which are often related to the plant source or properties. Thus, morphine was named after Morpheus (the God of sleep) and coniine derives from Conium maculatum (hemlock), the plant used in the judicial murder of Socrates (399 BC). Various chemical tests for alkaloids are used as preliminary indicators of alkaloid presence in crude plant extracts. Finally, it should be noted that alkaloids can also exist as jVoxides of the alkaloid base. 

Both of these alkaloids contain a quinoline group but the constitution as developed by a study of their reactions and products of oxidation is more complex than is desirable to discuss here. The relation of the two has been shown to be that brucine is a di-meth-oxy derivative of strychnine which agrees with the composition formulas as given. 

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