Alkaloid

Alkaloids are a large and diverse group of naturally occurring organic compounds that contain at least one nitrogen atom, most often within a heterocyclic ring. They are produced by a wide variety of organisms, including plants, fungi, bacteria, and certain animals, and many have potent physiological effects on humans and other animals. Because of their significant pharmacological activity, alkaloids occupy an important place in traditional medicine, modern pharmaceuticals, and biochemical research.

Definition and General Characteristics

Although the boundary between alkaloids and other nitrogen-containing compounds is not rigid, alkaloids are generally understood as nitrogenous, basic organic molecules of natural origin. They typically share the following features:

• Presence of nitrogen, usually in a heterocycle
• Physiological activity, often strong and specific
• Basic chemical behaviour, though neutral or weakly acidic alkaloids also exist
• Characteristic bitter taste
• Presence in plants, especially as secondary metabolites

In addition to carbon, hydrogen, and nitrogen, alkaloids may include oxygen or sulfur, and less commonly elements such as phosphorus, bromine, or chlorine. Compounds such as amino acids, peptides, nucleotides, amines, and antibiotics are generally not classed as alkaloids, although some borderline cases remain debated.

Naming Conventions

The term alkaloid was coined in 1819 by the German chemist Carl Friedrich Wilhelm Meissner. Many individual names reflect their botanical sources with the suffix -ine. Examples include:

• Atropine, from Atropa belladonna
• Strychnine, from Strychnos nux-vomica

When multiple alkaloids derive from a single plant, suffix variants such as -idine, -anine, or -inine help distinguish between them. More than eighty alkaloids bear the root vin- due to their derivation from Vinca species, forming the family of vinca alkaloids.

Historical Development

Alkaloid-containing plants have been used by humans since antiquity for medicinal, ritual, and sometimes toxic purposes. References to opium, ephedra, and coca appear in early civilisations from Mesopotamia to China and the Andes. Arrow poisons containing alkaloids such as aconitine and tubocurarine were employed in various cultures.
Scientific study accelerated in the nineteenth century:

• 1804: Friedrich Sertürner isolated morphine from opium, the first alkaloid to be obtained in pure form.
• 1818–1820: Pelletier and Caventou isolated strychnine and quinine.
• Other significant discoveries followed: xanthine (1817), atropine (1819), caffeine (1820), coniine (1827), nicotine (1828), colchicine (1833), sparteine (1851), and cocaine (1860).

By the late nineteenth century, synthetic chemistry contributed further progress. In 1886, Albert Ladenburg achieved the first complete laboratory synthesis of an alkaloid, producing coniine. Throughout the twentieth century, the development of chromatographic and spectroscopic techniques dramatically expanded knowledge of alkaloid structures and functions; by 2008, more than 12,000 alkaloids had been identified.

Classification

Alkaloids display immense structural diversity, and multiple overlapping classification schemes exist. The two most common approaches organise them by biosynthetic origin or by chemical structure.
Major groups include:

• True alkaloids: contain nitrogen within a heterocyclic ring and derive from amino acids. Examples: morphine, atropine, nicotine.
• Protoalkaloids: derive from amino acids but lack a heterocyclic nitrogen. Examples: mescaline, ephedrine, adrenaline.
• Polyamine alkaloids: derived from putrescine, spermidine, or spermine.
• Peptide and cyclopeptide alkaloids.
• Pseudoalkaloids: resemble alkaloids structurally but are not derived from amino acids. These include terpenoid and steroidal alkaloids as well as purine derivatives such as caffeine and theobromine.

Some compounds lie at classification boundaries—for example, nicotine contains both pyridine and pyrrolidine rings and can be assigned to more than one structural group.

Properties

Alkaloids vary widely in appearance and behaviour:

• Oxygen-containing alkaloids are generally crystalline solids.
• Oxygen-free forms, such as nicotine and coniine, tend to be oily, volatile liquids.
• Many are weak bases, forming characteristic salts with acids; a few are amphoteric.
• Solubility varies: free-base forms dissolve poorly in water but are readily soluble in organic solvents, while their salts are usually water soluble.

These properties allow alkaloids to be extracted from plant or microbial material using acid–base extraction, followed by purification through chromatographic methods.

Biological Activity and Uses

Alkaloids exhibit a wide range of pharmacological effects, many of which have been exploited in medicine:

• Antimalarial: quinine
• Bronchodilation: ephedrine
• Chemotherapy: omacetaxine
• Cholinomimetic: galantamine
• Vasodilatory: vincamine
• Antiarrhythmic: quinidine
• Analgesic: morphine
• Antibacterial: chelerythrine
• Antidiabetic: berberine