Introduction:

Most of the alkaloids are toxic to other organisms. They often encompass pharmacological effects and are employed as medications, as recreational drugs or in entheogenic rituals. Illustrations are the local anesthetic and stimulant, cocaine; the stimulant, caffeine; nicotine; the analgesic, morphine; the antibacterial, berberine; the anticancer compound, vincrinstine; the antihypertension agent, resepine; the cholinomimeric, galatamine; the spasmolysis agent,  atropine; the vasodilator, vincamine; the anti-arhythmia compound, quinidine; the anti-asthma therapeutic, ephedrine; and the antimalarial drug,  quinine. However, alkaloids act on the diversity of metabolic systems in humans and other animals; they approximately uniformly raise a bitter taste. 

Definition of Alkaloid:

Alkaloid is a group of naturally occurring chemical compounds that generally consists of basic nitrogen atoms. This group as well comprises some correlated compounds having neutral and even weakly acidic properties. As well some of the synthetic compounds of similar structure are attributed to alkaloids. Moreover to carbon, hydrogen and nitrogen, alkaloids might as well have oxygen, sulphur and more seldom other elements like chlorine, bromine and phosphorus. 

History of Alkaloid:

Alkaloid-containing plants were employed via humans since ancient times for therapeutic and recreational purposes. For illustration, medicinal plants have been acknowledged in the Mesopotamia at least around 2000 BC. The Odyssey of Homer referred to a gift provided to Helen via the Egyptian queen, a drug bringing oblivion. This is assumed that the gift was an opium-containing drug. A Chinese book on houseplants written in 1st-3rd centuries BC illustrated a medical use of Ephedra and opium poppies. As well coca leaves were employed by South American Indians since prehistoric times.

Studies of alkaloids started in the 19th century. In the year 1804, the German chemist Friedrich Serturner isolated from opium a 'soporific principle' (Latin:  principium somniferum), which he termed as 'morphium' in honor of  Morpheus, the  Greek  god of dreams; in German and several other Central-European languages, this is still the name of the drug. The word 'morphine', employed in English and French, was introduced by the French physicist Joseph Louis Gay-Lussac). 

An important contribution to the chemistry of alkaloids in the early years of its growth was made by the French researchers Pierre Joseph Pelletier and Joseph Bienaime Caventou who invented quinine in the year 1820 and strychnine in the year 1818. Some of the other alkaloids were invented around that time, comprising  xanthine  (1817),  atropine  (1819),  caffeine  (1820),  coniine  (1827), nicotine (1828), colchicine (1833), sparteine (1851) and cocaine (1860). 

The primary complete synthesis of an alkaloid was accomplished in the year 1886 by the German chemist Albert Ladenburg. He made coniine by reacting 2-methylpyridine by acetaldehyde and reducing the resultant 2-propenyl pyridine with sodium. The growth of the chemistry of alkaloids was accelerated via the emergence of spectroscopic and chromatographic processes in the 20th century, in such a way that by 2008 more than 12,000 alkaloids had been recognized. 

Properties of Alkaloid:

Most of the alkaloids have oxygen; those compounds are generally colorless crystals at ambient conditions. The oxygen-free alkaloids, like nicotine or coniine, are usually colorless, volatile, oily liquids. Some of the alkaloids are colored such as berberine (yellow) and sanguinarine (orange). 

Most of the alkaloid is weak bases; however some are amphoteric, for illustration theobromine and theophylline. Most of the alkaloids are poorly soluble in water however readily dissolve in the organic solvents, like diethyl ether, chloroform and 1,2-dichloroethane. Though, caffeine dissolves well in boiling water. By acids, alkaloids make salts of different strengths. Such salts are generally soluble in water and alcohol and poorly soluble in the most organic solvents. Exceptions comprise scopolamine hydrobromide that is soluble in organic solvents and water-soluble quinine sulphate. 

Most of the alkaloids encompass a bitter flavor. This is assumed that plants evolved the capability to produce such bitter substances, most of which are poisonous, in order to protect themselves from animals; though, animals in turn evolved the capability to detoxify alkaloids. Some of the alkaloids can generate developmental defects in the offspring of animals which use them but can't detoxify them. A characteristic illustration is the alkaloid cyclopamine that is present in the leaves of corn lily. Throughout the 1950s, up to 25% lambs born by sheep which had grazed on corn lily suffered serious facial defects. Such defects ranged from deformed jaws to cyclopia. After decades of research, in the year 1980, the substance which was responsible for the deformities were recognized as the alkaloid 11-deoxyjervine that was renamed cyclopamine. 

Distribution in Nature:

The alkaloid content in plants is generally in a few percent and is inhomogeneous over the plant tissues. Based on the kind of plants, the maximum concentration is noticed in the leaves (that is, black henbane), fruits or seeds (that is, Strychnine tree), root (that is, Rauwolfia serpentina) or bark (cinchona). Moreover, various tissues of the similar plants might have various alkaloids. 

Alongside plants, alkaloids are found in several kinds of fungi, like psilocybin in the fungus of the genus Psilocybe and in animals, like bufotenin in the skin of some toads. Most of the marine organisms as well have alkaloids. Some amines, like adrenaline and serotonin, which play an important role in higher animals, are identical to alkaloids in their structure and biosynthesis and are at times known as alkaloids. 

Extraction:

Due to the structural diversity of alkaloids, there is no single process of their extraction from natural raw materials. Most processes exploit the property of most alkaloids to be soluble in the organic solvents however not in water, and the opposite tendency of their salts.

Most of the plants have some alkaloids. Their mixture is extracted first and then individual alkaloids are separated. The plants are thoroughly ground prior to extraction. Most of the alkaloids are present in the raw plants in the form of salts of organic acids. The extracted alkaloids might remain as salts or modifies into bases. Base extraction is accomplished by processing the raw material by alkaline solutions and extracting the alkaloid bases by organic solvents, like 1,2-dichloroethane, chloroform, diethyl ether or benzene. Then, the impurities are dissolved through weak acids; this transforms alkaloid bases to salts which are washed away by water. If essential, an aqueous solution of alkaloid salts is again made alkaline and treated by an organic solvent. The method is repeated till the desired purity is accomplished.

The raw plant material, in the acidic extraction is processed via a weak acidic solution (example: acetic acid in water, ethanol or methanol). A base is then added to transform alkaloids to basic forms that are extracted by organic solvent (if the extraction was carried out by alcohol, it is eliminated first, and the remainder is dissolved in water). The solution is purified as illustrated above. 

The Alkaloids are separated from their mixture by employing their different solubility in some solvents and different reactivity by certain reagents or through distillation. 

Biosynthesis of Alkaloids:

The Biological precursors of most alkaloids are amino acids, like ornithine, tyrosine, lysine, phenylalanine, tryptophan, histidine, aspartic acid and anthranilic acid. Nicotinic acid can be synthesized from tryptophan or aspartic acid. Methods of alkaloid biosynthesis are too numerous and can't be simply categorized. Though, there are some typical reactions comprised in the biosynthesis of different classes of alkaloids, comprising synthesis of Schiff bases and Mannich reaction.

Synthesis of Schiff bases:

Schiff bases can be acquired by reacting amines by ketones or aldehydes. Such reactions are a common process of producing C=N bonds. 

Fig: Synthesis of Schiff bases

Mannich reaction:

The integral component of the Mannich reaction, in addition to the amine and a carbonyl compound, is a carbanion that plays the role of the nucleophile in the nucleophilic addition to the ion made up by the reaction of the amine and the carbonyl. 

Fig: Mannich reaction

Dimer alkaloids:

Moreover to the above illustrated monomeric alkaloids, there are as well dimeric and even trimeric and tetrameric alkaloids made up on condensation of two, three and four monomeric alkaloids. Dimeric alkaloids are generally made up from monomers of the similar kind via the given methods: 

• Mannich reaction, resultant in, example: voacamine
• Michael reaction (villalstonine)
• Condensation of aldehydes by amines (toxiferine).
• Oxidative addition of phenols (that is, dauricine, tubocurarine).
• Lactonization (carpaine).

The biological role of Alkaloids:

The role of alkaloids for living organisms that produce them is still uncertain. Primarily, it was supposed that the alkaloids are the final products of nitrogen metabolism in plants, as urea in mammals. Most of the recognized functions of alkaloids are associated to protection. For illustration, aporphine alkaloid liriodenine generated by the tulip tree protects it from parasitic mushrooms. Moreover, the presence of alkaloids in the plant prevents insects and chordate animals from eating it. Though, some of the animals adapted to alkaloids are even utilize them in their own metabolism. These alkaloid-related substances as serotonin, dopamine and histamine are significant neurotransmitters in animals. Alkaloids are as well acknowledged to regulate the plant growth.

Applications of Alkaloids:

In medicine:

The medical use of alkaloid plants consists of a long history and therefore whenever the first alkaloids were synthesized in the nineteenth century, they instantly found application in clinical practice. Most of the alkaloids are still employed in medicine, generally in the form of salts, comprising the following:

Alkaloid                      Action

Ajmaline                    antiarrhythmic

Codeine                    cough medicine

Cocaine                     anesthetic

Colchicine                  remedy for gout

Morphine                   analgesic

Reserpine                  antihypertensive

Tubocurarine             Muscle relaxant

Physostigmine           Inhibitor of acetylcholinesterase

Quinidine                  antiarrhythmic

Quinine                     antipyretics, antimalarial

Emetine                    antiprotozoal agent

Ergot alkaloids          sympathomimetic, vasodilator, antihypertensive

Most of the synthetic and semi-synthetic drugs are structural modifications of the alkaloids that were designed to improve or change the main effect of the drug and decrease unwanted side effects.

For illustration: naloxone, an opioid receptor antagonist, is the derivative of thebaine that is present in opium. 

In agriculture:

Previous to the growth of a broad range of relatively low-toxic synthetic pesticides, some of the alkaloids, like salts of nicotine and anabasine, were employed as insecticides. Their use was restricted by their high toxicity to humans.

Use as psychoactive drugs:

The preparations of plants having alkaloids and their extracts and later pure alkaloids have long been employed as psychoactive substances. Cocaine and cathinone are the stimulants of central nervous system. Mescaline and most of indole alkaloids (like psilocybin, dimethyltryptamine and ibogaine) have hallucinogenic effect. The Morphine and codeine are strong narcotic pain killers. 

There are alkaloids which don't encompass strong psychoactive effect themselves; however are precursors for the semi-synthetic psychoactive drugs. For illustration, ephedrine and pseudoephedrine are employed to produce methamphetamine and methcathinone.

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