_Nicotine_, the alkaloid of tobacco, was discovered by Posselt and Reimann in 1828. Its constitution was first ascertained by Pinner, and it was synthetically obtained by Amé Pictet, in 1904, as an inactive substance, capable of being resolved by the crystallisation of its tartrates into a dextro- and lævo-modification, the latter of which was identical with that found in the tobacco leaf.
_Atropine_ and _hyoscyamine_—the poisonous principles of belladonna and henbane—are isomeric alkaloids, the former of which is optically inactive, and the latter is lævo-rotatory. Atropine is, in fact, the racemic modification. The constitution of both alkaloids is known, and their synthesis is now possible.
The successive steps may be thus indicated:
1. _Synthesis of glycerin_ (Faraday, Kolbe, Melsens, Boerhave, Friedel, and Silva).
2. _Glycerin to glutaric acid_ (Berthelot and De Luca, Cahours and Hofmann, Erlenmeyer, Lermantoff, and Markownikoff).
3. _Glutaric acid to suberone_ (Brown and Walker, Boussingault).
4. _Suberone to tropidine_ (Willstätter).
5. _Tropidine to tropine_ (Willstätter, Ladenburg).
6. _Synthesis of tropic acid_ (Berthelot, Fittig and Tollens, Friedel, Ladenburg, and Rügheimer).
7. _Tropine and tropic acid: atropine_ (Ladenburg).
The alkaloid _cocaïne_, contained in the leaves of _erythroxylon coca_ and now employed as a local anæsthetic, was discovered by Niemann in 1860. It has been shown to be closely related to atropine in constitution, and has now been synthetically prepared in the dextro-modification.
The alkaloids _papaverine_, _narcotine_, _narceïne_, contained in opium, are derivatives of _iso_quinoline, as also is _berberine_, found in the common barberry (_berberis vulgaris_). Papaverine, which occurs in opium to the extent of about one per cent., was first isolated by Merck in 1848. Its constitution has been established by Goldschmidt. _Narcotine_ is, next to morphine, the most abundant constituent of opium. The study of the products of its hydrolysis and oxidation—viz., _opianic acid_ and _cotarnine_, both of which substances have long been known—has indicated its probable structure. _Narceïne_ is closely allied to narcotine, and can, indeed, be obtained from it by combining the latter alkaloid with methyl iodide and treating the compound with caustic potash. The constitution of _berberine_, which is one of the few coloured vegeto-alkaloids known, has been worked out by Perkin. As yet nothing definite is known concerning the structure of the most important and largest constituent of opium—viz., _morphine_; or of its congeners _codeïne_ and _thebaine_. Grimaux, however, in 1881 converted morphine into codeïne by treatment with methyl iodide and potash; hence the two alkaloids stand in a relation somewhat similar to that in which narceïne stands to narcotine. There is very little doubt that the three alkaloids are very closely related, and that a knowledge of the constitution of one of them would immediately elucidate the structure of the others. They are probably phenanthrene derivatives.