Alkaloids

Alkaloids

A precise definition of the term ‘alkaloid’ (alkali-like) is somewhat difficult because there is no clear-cut boundary between alkaloids and naturally occurring complex amines. Typical alkaloids are derived from plant sources, they are basic, they contain one or more nitrogen atoms (usually in a heterocyclic ring) and they usually have a marked physiological action on man or other animals. The name ‘proto-alkaloid’ or ‘amino-alkaloid’ is sometimes applied to compounds such as hordenine, ephedrine and colchicine which lack one or more of the properties of typical  alkaloids. Other alkaloids, not conforming with the general definition, are those synthetic compounds not found in plants but very closely related to the natural alkaloids (e.g. homatropine). In practice, those substances present in plants and giving the standard qualitative tests outlined below are termed alkaloids, and frequently in plant surveys this evidence alone is used to classify a articular plant as ‘alkaloid-containing’.

HISTORY

The first isolations of alkaloids in the nineteenth century followed the reintroduction into medicine of a number of alkaloid-containing drugs and were coincidental with the advent of the percolation process for the extraction of drugs. The French apothecary Derosne probably isolated

the alkaloid afterwards known as narcotine in 1803 and the Hanoverian apothecary Sertürner further investigated opium and isolated morphine (1806, 1816). Isolation of other alkaloids, particularly by Pelletier and Caventou, rapidly followed; strychnine (1817), emetine (1817), brucine (1819), piperine (1819), caffeine (1819), quinine (1820), colchicines (1820) and coniine (1826). Coniine was the first alkaloid to have its structure established and to be synthesized, but for others, such as colchicine, it was well over a century before the structures were finally elucidated. Modern methods and instrumentation have greatly facilitated these investigations, and it is interesting to note that the yields of ‘minor’ alkaloids, too small for further investigation, isolated by chemists during the first quarter of the last century would now be sufficient, several thousand times over, for a complete structure analysis. In the second half of the twentieth century

alkaloids featured strongly in the search for plant drugs with anticancer activity. A notable success was the introduction of Catharanthus alkaloids and paclitaxel into medicine and there is much current interest in other alkaloids having anticancer properties as well as those exhibiting antiaging and antiviral possibilities.

PROPERTIES

Most alkaloids are well-defined crystalline substances which unite with acids to form salts. In the plant they may exist in the free state, as salts or as N -oxides (see below). In addition to the elements carbon, hydrogen and nitrogen, most alkaloids contain oxygen. A few, such as coniine from hemlock and nicotine from tobacco, are oxygen-free and are liquids. Although coloured alkaloids are relatively rare, they are not unknown; berberine, for example, is yellow and the salts of sanguinarine are copper-red.

A knowledge of the solubility of alkaloids and their salts is of considerable pharmaceutical importance. Not only are alkaloidal substances often administered in solution, but also the differences in solubility between alkaloids and their salts provide methods for the isolation of alkaloids from the plant and their separation from the nonalkaloidal substances also present. While the solubilities of different alkaloids and salts show considerable variation, as might be expected from their extremely varied structure, it is true to say that the free bases are frequently sparingly soluble in water but soluble in water but soluble in organic solvents; with salts the reverse is often the case, these being usually soluble in water but sparingly soluble in organic solvents.

For example, strychnine hydrochloride is much more soluble in water than is strychnine base. It will soon be realized that there are many exceptions to the above generalizations, caffeine (base) being readily extracted from tea with water and colchicine being soluble in either acid, neutral or alkaline water. Again, some alkaloidal salts are sparingly soluble—for example, quinine sulphate is only soluble to the extent of 1 part in 1000 parts of water, although 1 part quinine hydrochloride is soluble in less than 1 part of water.

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