Alkaloids
Authors: Dalton David R. , Mascavage Linda M. , Wilson Michael 
Published: July 2004

AbstractAlkaloids are not simply defined. However, most scientists working in the field of alkaloid chemistry would agree that most alkaloids, in addition to being products of secondary metabolism, are organic nitrogen‐containing bases of complex structure; many have physiological activity. Current compendia of alkaloids list compounds that, for the most part, occur in flowering plants. However, as detection methods improve it is almost certain that some concentration of alkaloids will be found almost everywhere. For example, in addition to flowering plants, alkaloids have also been found in birds, butterflies and beetles; in millipedes and in algae and fungi. Even in humans, it appears that trace quantities of alkaloids are naturally occurring components of cerebrospinal fluid. Usually, alkaloids are thought of as minor plant constituents and are present in only miniscule quantities in animals. Initially, the search for alkaloids in plant material depended on reports of specific plant use for definite purposes or observations of the effect specific plants had on indigenous animals. Newer methods of analysis (eg, mass spectrometry) are now employed. Until separation techniques such as chromatography and countercurrent extraction had advanced sufficiently to be of widespread use, only the major alkaloids could be isolated (and purified) from plant extracts. With the improvement in isolation techniques, materials of physiological significance, even when present in very low concentrations, can be obtained in commercial quantities. Major strides in plant genomics are introducing possibilities of biotransformations to generate alkaloids not previously found as well as adjusting concentrations of the various alkaloids known to be present. Since most alkaloids are basic they are generally separated from accompanying neutrals and acids by extraction with dilute mineral acid. The purified bases tend to be colorless and crystalline, with definite melting points. Most are chiral. The building blocks of primary metabolism from which the large majority of alkaloids stem include the common amino acids ornithine, lysine, phenylalanine, tyrosine, and tryptophan. The simple pyrrolidine alkaloids as well as the widely found pyrrolizidine alkaloids and the bicyclic tropane bases such as atropine, scopolamine, and cocaine are all derived from the same precursor, ornithine. The simple monocyclic bases and their more elaborate polycyclic relatives found in pomegranate and various members of the common generaSedumandLycopodium, are derived from the amino acid lysine. Nicotine as well as its less common relatives such as anabasine, are commonly found only in various tobaccos. There are a relatively large number of alkaloids that may be considered as derived from phenethylamine, C6H5CH2CH2NH2, or tyramine,p‐HOC6H4CH2CH2NH2. These bases are, in turn, considered derived from phenylalanine and tyrosine. The alkaloids derived from them include relatively simple monocyclic bases such as mescaline. Just as for norbelladine (or its enzyme bound equivalent) serving as the precursor for the C6–C2+ C6–C1family of alkaloids, so it is that Norlaudanosoline (or its enzyme bound equivalent) is considered the progenitor for the very large number of C6–C2+ C6–C2bases common, among others, in the opium poppy (Papaver Somniferum) including codeine and morphine. There are volumes written exclusively on alkaloids known to be derived from the amino acid tryptophan with and without additional carbon framework. The simpler alkaloids include serotonin. However, the addition of a five carbon unit (from mevalonic acid) yields lysergic acid, and a ter carbon unit (from loganin, itself derived from two units of mevalonic acid) yields the related materials strychnine and quinine. Many alkaloids such as atropine and reserpine that have served humanity since early history as pallatives are being replaced by synthetic materials. Others, such as theVincabases, eg, vincristine, remain as powerful medical tools. There are currently four broad classes of alkaloids and/or materials whose alkaloid content is considered important enough to be of sizeable economic value. As a consequence, markets are made, treaties and alliances formed, etc, regarding the opiates, such as morphine and codeine; cocaine, licit and illicit; caffeine and related bases in coffee and tea; and the tobacco alkaloids such as nicotine.