The Nature and Definition of an Alkaloid

Pelletier, S. W. (1983). The nature and definition of an alkaloid. Alkaloids, Chemical and Biological Perspectives 1,1-31. 

For one view of what constitutes an alkaloid see Pelletier, S. W. The Nature and Definition of an Alkaloid Alkaloids Chemical and Biological Perspectives, Pelletier, S. W., Ed. John Wiley and Sons, 1982, Vol. 1, pp 1-31. 

Up to now about 80 alkaloids have been isolated. Some of them exert a hypoglycae-mic effect, verifying their use in traditional medicine as an antidiabetic drug. During the investigation of the hypoglycaemic effect of some alkaloid fractions it was found that they had decreased the number of leucocytes in the circulating blood and there was also an inhibition of erythropoesis in the bone marrow. This important observation led to the discovery of the tumour inhibitory effect. Four (two natural and two semi-synthetic) alkaloids are used in the treatment of definite forms of tumours. These alkaloids occur in the leaves in very low concentration. To obtain 1 g of pure alkaloid, about 500 kg of dried leaves must be extracted. 

Returning to the question in the title of this section, capsaicin does not fall into any of the three classic types of nitrogen-bearing plant natural products, being neither a true alkaloid, a protoalkaloid, or a pseudoalkaloid. Capsaicin is oflimited distribution in Nature and shows pharmacological activity, but is non-basic, structurally unsophisticated, and not directly derived from an amino acidic precursor. On the other hand, the lack of attributes such as basicity, complexity, and an amino acidic pedigree can also be found in compounds commonly perceived as alkaloids. Thus, colchicine is neutral, ephedrine is structurally unsophisticated, and the nitrogen atom of the potato alkaloid solanine is not derived from an amino acid, but rather incorporated into as non-amino acidic framework by a transamination reaction. For the sake of clarity and consistency, it seems therefore convenient to adopt the modern definition of alkaloids, and consider capsaicin, as well as alkylamides such as piperine (18) and pellitorine (19), as such. 

Alkaloids represent one of the largest class of natural products with over 12000 defined structures [1], They can be summarized as nitrogen containing, mostly N-heterocyclic substances whose carbon skeleton is derived from amino acids. In a broader definition this group includes proto- and pseudoalkaloids and a number of microbial metabolites that are usually classified as antibiotics. In this review a broad definition of what to consider an alkaloid was chosen, albeit the emphasis is on alkaloids sensu strictu. 

Following the partial and total syntheses of a-isosparteine, the natural occurrence of Z-a-isosparteine in Lupinus cavdatus Kellogg was definitely established (310). More recently, the identity of Z-a-isospar-teine with genisteine has been confirmed (312). Genisteine was first considered, erroneously, to be an alkaloid of composition C16H28N2 (45, 46, 271), isolated from Cytisus scoparius L. For direct comparison and identification, recourse was had to additional derivatives aurichloride,... 

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