Strychnine and Brucine

Glandular products, drugs of vegetable origin, such as quinine, strychnine and brucine, emetine, and digitalis glycosides ... 

S. cinnamomifolia Thwaites (Ceylon, India). Strychnine and brucine (Short, Year-hook Pharm., 1924, 646). 

It is not certain that the rest of the molecule in these two alkaloids is identical in structure with that in strychnine and brucine. 

While this work was in progress Spath and Bretschneider showed that strychnine, on oxidation with permanganate in alkaline solution, furnished W-oxalylanthranilic acid (VII), brucine yielding oxalyl-4 5-dimethoxy-anthranilic acid, the latter observation providing confirmation of the evidence previously adduced that the two methoxy-groups in brucine are in the oj Ao-position relative to each other as indicated by Lions, Perkin and Robinson. The results so far considered indicate the presence in brucine and strychnine of the complex (VIII), which can be extended to (IX) if account is taken of the readiness with which carbazole can be obtained from strychnine and brucine and certain of their derivatives by decomposition with alkali at temperatures ranging from 200° to 400°, Knowledge of the structure of the rest of the molecule is mainly due to the results of the exhaustive study by Leuchs and his pupils of the oxidation... 

Three new papers bearing on the structure of strychnine have become available too late for inclusion in this summary of recent work. Woodward, Brehm and Nelson have compared the ultra-violet absorption spectra of strychnine and Leuchs s strychnone (p.. 559) and used the results for a discussion of the relationship of the two alkaloids. Prelog and Kathriner have investigated the oxidation of strychnine, i/t-strychnine and brucine by permanganate in weakly acid solution and Bailey and Robinson from a study of the brucones have confirmed the conclusion of Woodward et al. that Leuchs s strychnone is a true indole derivative. Mention must also be made of a paper by Clemo and King on new reduction products of strychnine, of which a preliminary account has been published with a summary of the ensuing discussion. 

Fig. 1 Reflectance scan of a nux vomica extract (A) and a reference chromatogram containing 1 gg each of strychnine and brucine (B). Start (1), brucine (2), strychnine (3), front (4).

Gharagozloo P, Lazareno S, Popham A, Birdsall N. Allosteric interactions of quaternary strychnine and brucine derivatives with muscarinic acetylcholine receptors. J Med Chem 1999 42 438-445. 

Strychnine and brucine are extremely toxic alkaloids. Strychnine binds itself to receptor sites in the spinal cord and accommodates glycine. Brucine is a dimethoxy form of strychnine, and is less toxic. 

Frederich, M., Choi, Y. H. and Verpoorte, R. 2003. Quantitative analysis of strychnine and brucine in Strychnos nux-vomica using H-NMR. Planta Medica, 69 1169-1171. 

Bertrand Pelletier, 1761-1797. French chemist and pharmacist who investigated the arsenates, phosphates, and phosphides of many metals, studied the action of phosphorus on platinum, and devised new methods for making soap and refining metal for clocks. He served as inspector of the hospitals m Belgium. His son, Joseph Pelletier (1788-1842), and Joseph Caventou discovered quinine, cmehomne, strychnine, and brucine. See also ref. (89). 

In recent years, considerable attention has been paid to the 13C n.m.r. spectra of strychnine and brucine. Two recent papers810,6 were prompted by errors and inconsistencies in earlier contributions on this topic it is to be hoped that the assignments now made are completely reliable. 

In many cases, amino acids can be resolved by the methods we have already discussed (Section 5-16). If a racemic amino acid is converted to a salt with an optically pure chiral acid or base, two diastereomeric salts are formed. These salts can be separated by physical means such as selective crystallization or chromatography. Pure enantiomers are then regenerated from the separated diastereomeric salts. Strychnine and brucine are naturally occurring optically active bases, and tartaric acid is used as an optically active acid for resolving racemic mixtures. 

Strychnine and brucine have been the subject of a very large number of degradative researches, nearly all of them before the advent of modern spectroscopic techniques, and the elucidation of their structure represents one of the major achievements of classical organic chemistry. The... 

Chromic acid in aqueous sulfuric acid attacks the benzene ring in a large number of strychnine and brucine derivatives, leading to the isolation of products in which the aromatic ring has been oxidized away. Doubtless, as the low yields indicate, attack of the other, nonaromatic, portion of the molecules also occurs, but this is presumably so indiscriminate that the isolation of homogeneous products has so far failed. The following is a selection of the more important and interesting chromic acid oxidations. 

The strychnine and brucine sulfonic acids, which probably contain a sulfonic acid group on a carbon a to Nb, are oxidized to products which correspond to sulfonic acids of the Ci6 and C17 acids (117, 118). 

Of the methods for the separation of racemic mixtures into dieir components one of the most useful is the formation of salts with optically active acids or bases. Early attempts to apply this method to the amino acids failed, since these compounds are not only weak acids, and therefore form rather unstable salts widi bases, but are also weak bases, and form unstable salts with acids. Fischer overcame this difficulty by converting the amino acids into their benzoyl derivatives, which he found to be stronger acids and so formed stable salts with optically active bases such as the alkaloids strychnine and brucine. Ordinary methods of benzoylation failed in this instance, but good yields were obtained in the presence of sodium bicarbonate. 

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