Secondary Plant Products
Secondary Metabolites: An Introduction
Secondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of organisms. Unlike primary metabolites, absence of secondary metabolites does not result in immediate death, but rather in long-term impairment of the organism's survivability, fecundity, or aesthetics, or perhaps in no significant change at all. Secondary metabolites are often restricted to a narrow set of species within a phylogenetic group. Secondary metabolites often play an important role in plant defence against herbivory and other interspecies defences.
Categories
Most of the secondary metabolites of interest to humankind fit into categories which classify secondary metabolites based on their biosynthetic origin. Since secondary metabolites are often created by modified primary metabolite syntheses, or borrow substrates of primary metabolite origin, these categories should not be interpreted as saying that all molecules in the category are secondary metabolites (for example the steroid category), but rather that there are secondary metabolites in these categories.
Microscale molecules
Alkaloids usually a small, heavily derivatised amino acid:
Hyoscyamine, present in Datura stramonium
Atropine, present in Atropa belladonna, Deadly nightshade
Cocaine, present in Erythroxylon coca the Coca plant
Codeine and Morphine, present in Papaver somniferum, the opium poppy
Tetrodotoxin, a microbial product in Fugu and some salamanders
Vincristine & Vinblastine, mitotic inhibitors found in the Rosy Periwinkle
Terpenoids come from semiterpene oligomerization:
Azadirachtin - Neem tree.
Artemisinin, present in Artemisia annua Chinese wormwood
tetrahydrocannabinol, present in cannabis sativa
Steroids (Terpenes with a particular ring structure)
Saponins - plant steroids, often glycosylated
Glycosides (heavily modified sugar molecules):
Nojirimycin
Glucosinolates
Phenols:
Resveratrol
Phenazines:
Pyocyanin
Phenazine-1-carboxylic acid (and derivatives)
Larger-scale molecules
Polyketides:
Erythromycin
Discodermolide
Fatty acid synthase products :
FR-900848
U-106305
phloroglucinols
Nonribosomal peptides:
Vancomycin
Thiostrepton
Ramoplanin
Teicoplanin
Gramicidin
Bacitracin
Hybrids of the above three:
Epothilone
Polyphenols
Non-'small molecules' - DNA, RNA, ribosome, or polysaccharide classical biopolymers
Ribosomal peptides:
Microcin-J25
Toxic By-products
Cochicine
Colchicine is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum. It was used originally to treat rheumatic complaints, especially gout, and still finds use for these purposes today despite dosing issues concerning its toxicity. It was also prescribed for its cathartic and emetic effects. Colchicines’ present medicinal use is in the treatment of gout and familial Mediterranean fever; it can also be used as initial treatment for pericarditis and preventing recurrences of the condition. It is also being investigated for its use as an anticancer drug. In neurons, axoplasmic transport is disrupted by colchicine.
Alkaloids
Alkaloids are a group of naturally occurring chemical compounds which mostly contain basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. Beside carbon, hydrogen and nitrogen, molecules of alkaloids may contain sulphur and rarely chlorine, bromine or phosphorus.
Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of the group of natural products. Many alkaloids can be purified from crude extracts by acid-base extraction. Many alkaloids are toxic to other organisms. They often have pharmacological effects and are used as medications, as recreational drugs, or in entheogenic rituals. Examples are the local anesthetic and stimulant cocaine, the stimulant caffeine, nicotine, the analgesic morphine, or the antimalarial drug, quinine. Although alkaloids act on a diversity of metabolic systems in humans and other animals, they almost uniformly invoke a bitter taste.
The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut. Compounds like amino acid peptides, proteins, nucleotides, nucleic acid, amines and antibiotics are usually not called alkaloids. Natural compounds containing nitrogen in the exocyclic position are usually attributed to amines rather than alkaloids. Some authors, however, consider alkaloids a special case of amines.
Biological precursors of most alkaloids are amino acids, such as ornithine, lysine, phenylalanine, tyrosine, tryptophan, histidine, aspartic acid and anthranilic acid; all these amino acids, except anthranilic acid, are proteinogenic that is they are contained in proteins. Nicotinic acid can be synthesized from tryptophan or aspartic acid. Ways of alkaloid biosynthesis are too numerous and can not be easily classified. However, there is a few typical reactions involved in the biosynthesis of various classes of alkaloids, including synthesis of Schiff bases and Mannich reaction.
Synthesis of Schiff Bases
Schiff bases can be obtained by reacting amines with ketones or aldehydes. These reactions are a common method of producing C=N bonds.
In the biosynthesis of alkaloids, such reactions may take place within a molecule, such as in the synthesis of piperidine:
Mannich reaction
In integral component of the Mannich reaction, in addition to an amine and a carbonyl compound, is a carbanion, which plays the role of the nucleophile in the nucleophilic addition to the ion formed by the reaction of the amine and the carbonyl.
The Mannich reaction can proceed both intermolecularly and intramolecularly:
Dimer alkaloids
In addition to the described above monomeric alkaloids, there are also dimeric, and even trimeric and tetrameric alkaloids formed upon condensation of two, three and four monomeric alkaloids. Dimeric alkaloids are usually formed from monomers of the same type through the following mechanisms:
Mannich reaction, resulting in, e.g. voacamine
Michael reaction (villalstonine).
Condensation of aldehydes with amines (toxiferine).
Oxidative addition of phenols (dauricine and tubocurarine).
Lactonisation (carpaine).
Secondary byproducts in more detail
Phytotoxin
Phytoxin refers to a substance produced by a plant that is toxic or a substance that is toxic to the plant. Many substances produced by plants are secondary metabolites and are the by-products of primary physiological processes. Some examples of phytotoxins are alkaloids, terpenes, phenolics, herbicides and substances produced by bacteria.
Alkaloids
Alkaloids are derived from amino acids, and contain nitrogen. They are medically important by interfering with components of the nervous system affecting membrane transport, protein synthesis, and enzyme activities. They generally have a bitter taste. Alkaloids usually end in “ine” (caffeine, nicotine, cocaine, morphine, and ephedrine).
Terpenes
Terpenes are made of water insoluble lipids, and synthesised from acetyl CoA or basic intermediates of glycolysis. They often end in -ol (menthol) and make the majority of plant essential oils.
Monoterpenes are found in gymnosperms and collect in the resin ducts and maybe released after an insect begins to feed to attract the insect's natural enemies.
Sesquiterpenes are bitter tasting to humans and are found on glandular hairs or subdermal pigments.
Diterpenes are contained in resin and block and deter insect feeding. Taxol, an important anticancer drug is found in this group.
Triterpenes mimic the insect molting hormone ecdysone, disrupting molting and development and is often lethal. They are usually found in citrus fruit, and produce a bitter substance called limonoid that deters insect feeding.
Glycosides are made of one or more sugars combined with a non-sugar like aglycone, which usually determines the level of toxicity. Cyanogenic glycosides are found in many plant seeds like cherries, apples, and plums. Cyanogenic glycosides produce cyanide and are extremely poisonous. Cardenolides have a bitter taste and influence NA+/K+ activated ATPases in human heart, they may slow or strengthen the heart rate. Saponins have lipid and water soluble components with detergent properties. Saponins form complexes with sterols and interfere with their uptake.
Phenolics
Phenolics are made of a hydroxyl group bonded to an aromatic hydrocarbon. Furanocoumarin is a phenolic and is non-toxic until activated by light. Furanocoumarin blocks the transcription and repair of DNA. Tannins are another group of phenolics and they are important in tanning leather. Lignins, also a group of phenolics, is the most common compound on earth and helps conduct water in plant stems and fill spaces in the cell.
Glucosinolates are anions that occur only in the cells of a limited number of dicotyledonous families. Glucosinolates are very common in the order Capparales (best-known family: Brassicaceae) where they occur in every species hitherto examined. Among the best-known representatives are the active ingredients of horse-radish, radish and mustard. The elimination of aliphatic Glucosinolates in rape achieved by cultivation resulted in so-called double zero varieties (00-varieties). The cultivation of simple zero varieties is based on the elimination of erucid acid, a long-chained unsaturated fatty acid.
The first record mentioning the use of rubber goes back to the 11th century. Since this time, the Indians of Middle America use rubber balls in their ball games. From a chemical point of view rubber is a carbohydrate consisting of high molecular weight chains of 1, 4 - polyisoprene residues in cis-configuration (caoutchouc). The main source is Hevea brasiliensis. Gutta-percha consists of 1,4 - polyisoprene residues in trans-configuration. Its molecular weight is far below that of rubber. The main source is Palaquium gutta. A similar substance, balata, is obtained from Mimosops balata.
Chicle
Chicle (obtained from Achras sapota), finally, is a polymer containing both cis- and trans-bonds (in the ratio 1:2). It is the basic substance of bubble gum. Altogether, more than 1800 plant polyisoprenes have been identified. Their cellular concentrations are usually small, and their molecular weights are relatively low.
Polyisoprenes
Polyisoprenes occur in certain plant cells as small latex particles. They can be seen in the electron microscope as clearly defined, cytoplasmatic inclusions specific for the respective species.
Plant amines are derivatives of ammonia. Their collective structures are:
primary amines: NH2R
secondary amines: NHRR'
tertiary amines: NRR'R''
quaternary amines: N+RR'R''R'''(OH-)
A wide range of plant amines can be found in the most different plant cells. They are usually generated by the decarboxylation of amino acids or by transamination of aldehydes. The distinction between plant amines and alkaloids is sometimes a little arbitrary. Some, like mescaline, are counted among the alkaloids although in a chemical sense they are amines.
Aliphatic amines are often produced during anthesis, i.e. the opening of a flower or the formation of the fruiting body of certain fungi (like the stinkhorn, for example). They are insect-attractants. A good example of insect attractants is the aliphatic-aromatic amines in Araceae (lords-and-ladies, arum and others).
Among the di- and polyamines are putrescine (NH2(CH2)4NH2), as well as spermidine (NH2(CH2)3NH(CH2)4NH2) and spermine (NH2(CH2)3NH(CH2)4NH(CH2)3NH2). They occur in nearly all eucaryotic cells and interact with the DNA double helix. Among the tryptamines are the phytohormone indole-3-acetic acids (IAA) as well as serotonin.
Plant Secondary Metabolites: Sources and Effects
Carotenoids
Carotenoids are organic pigments occurring in plants and are mostly found in red, orange and yellow fruits and vegetables. Other vegetables such as broccoli, spinach or curly kale also contain carotenoids. Carotenoids have antioxidative effects and prevent cancer. In addition to this they boost the immune system and reduce the risk of getting heart attacks.
Phytosterols
Phytosterols are found in plant foods such as sunflower seeds, sesame, nuts and Soya beans. Phytosterols protect against colon cancer and lower cholesterol levels. Phytosterols are chemically similar to cholesterol and therefore they compete against each other for absorption in the body.
Saponins
Saponins are flavour additives, which are found in legumes and spinach. Saponins boost the immune system, lower the cholesterol levels in the blood and reduce the risk of getting intestinal cancer.
Glucosinolates
Glucosinolates are flavour additives, which are found in all types of cabbages, mustard, radish and cress. Glucosinolates prevent infections and inhibit the development of cancer.
Flavonoids
Flavonoids are organic pigments occurring in plants which give plants a red, violet or blue colour. Flavonoids have a particularly broad spectrum of efficacy. Flavonoids inhibit the growth of bacteria and viruses, protect the cells against the damages of free radicals, protect against cancers and heart attacks, have a repressive effect against inflammations and they influence blood coagulation.
Protease-inhibitors
Protease-inhibitors are found in plants that are rich in protein such as legumes, potatoes and wheat and they inhibit the decomposition of protein. Protease inhibitors protect the body against cancers and regulate the blood sugar levels.
Terpenes
Terpenes are plant flavours for e.g. the menthol in peppermint oil or the essential oils in herbs and spices. Terpenes decrease the risks of cancer.
Phytoestrogens
Phytoestrogens are natural plant hormones which are similar to the sexual hormones. Phytoestrogens are mostly found in wheat, legumes and wheat products. Phytoestrogens protect the body against hormonal dependant cancers such as breast, uterine and prostrate cancer.
Sulphides
Sulphides are compounds containing sulphur which are mostly found in plants that belong to the lily family such as onions, leeks, asparagus and garlic. Sulphides inhibit the growth of bacteria, lower cholesterol levels, protect the body from free radicals and have preventive effects against cancer.
Phytic acid
Phytic acid is found in wheat, legumes and flaxseeds. Phytic acid was considered undesirable for a long time because it binds trace elements such as iron and zinc and it also affects various digestive enzymes. However new studies have proved that Phytic acid has an antioxidant effect in the large intestine.
Substances Toxic to Plants
Herbicides
Herbicides usually interfere with plant growth and often imitate plant hormones.
ACCase Inhibitors kill grasses and inhibit the first step in lipid synthesis, acetyl CoA carboxylase, thus affecting cell membrane production in the meristem. They do not affect dicots plants.
ALS Inhibitors affect grasses and dicots by inhibiting the first step in some amino acid synthesis, acetolactate synthesis. The plants are slowly starved of theses amino acids and eventually DNA synthesis stops.
ESPS Inhibitors affect grasses and dicots by inhibiting the first step in the synthesis of tryptophan, phenylalanine and tyrosine, enolpyruvylshikimate 3-phosphate synthase enzyme.
Photosystem II Inhibitors reduce the electron flow from water to NADPH2+ causing electrons to accumulate on chlorophyll molecules and excess oxidation to occur. The plant will eventually die.
Synthetic Auxin mimics plant hormones and can affect the plant cell membrane.
Bacterial Phytotoxins
Tabtoxin is produced by Pseudomonas tabaci that may cause toxic concentrations of ammonia to build up. This build up of ammonia causes leaf chlorosis.
Glycopeptides are produced by a number of bacteria and have been indicated in disease development. A glycopeptide from Corynebacterium sepedonicum causes rapid wilt and marginal necrosis. A toxin from Corynebacterium insidiosum causes plugging of the plant stem interfering with water movement between cells. Amylovorin is a polysaccharide from Erwinia amylovora and causes wilting in rosaceous plants. A polysaccharide from Xanthomonas campestris obstructs water flow through phloem causing black rot in cabbage.
Phaseotoxins produced by Pseudomonas phaseolicola and Pseudomonas glycinea can cause starch accumulation, decrease cell permeability in swiss chard and inhibit bean callus tissue growth.
Rhizobiotoxine produced by Rhizobium japonicum causes the root nodules of some soy bean plants to become chlorotic.
Neonicotinoids and the decline of bees
Neonicotinoids are a class of neuro-active insecticides chemically similar to nicotine. In the 1980s Shell and in the 1990s Bayer started work on their development. The neonicotinoid family includes acetamiprid, clothianidin, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam. Imidacloprid is the most widely used insecticide in the world. Compared to organophosphate and carbamate insecticides, neonicotinoids cause less toxicity in birds and mammals than insects.
Some breakdown products are also toxic to insects. Neonicotinoid use has been linked in a range of studies to adverse ecological effects, including honey-bee colony collapse disorder (CCD) and loss of birds due to a reduction in insect populations; the findings used to be conflicting and thus controversial , but recent studies by the EFSA have confirmed the risk to bees. In 2013, the European Union and a few non EU countries restricted the use of certain neonicotinoids. In 2018, the EU banned the three main neonicotinoids (clothianidin, imidacloprid and thiamethoxam) for all outdoor uses. Several states in the United States have also restricted usage of neonicotinoids out of concern for pollinators and bees.
Essential oils
An essential oil is a concentrated, hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile, ethereal oils or aetherolea, or simply as the "oil of" the plant from which they were extracted, such as oil of clove. An oil is "essential" in the sense that it carries a distinctive scent, or essence, of the plant. Essential oils do not as a group need to have any specific chemical properties in common, beyond conveying characteristic fragrances.
Essential oils are generally extracted by distillation. Other processes include expression, or solvent extraction. They are used in perfumes, cosmetics, soap and other products, for flavouring food and drink, and for scenting incense and household cleaning products.
Various essential oils have been used medicinally at different periods in history. Medical application proposed by those who sell medicinal oils range from skin treatments to remedies for cancer, and are often based on historical use of these oils for these purposes. Such claims are now subject to regulation in most countries, and have grown vaguer to stay within these regulations.
Interest in essential oils has revived in recent decades with the popularity of aromatherapy, a branch of alternative medicine which claims that the specific aromas carried by essential oils have curative effects. Oils are volatilised or diluted in carrier oil and used in massage, diffused in the air by a nebuliser or by heating over a candle flame, or burned as incense, for example.
The techniques and methods first used to produce ethereal oil was first mentioned by Ibn al-Baitar (1188-1248), an Andalusian physician, pharmacist and chemist.
Most flowers contain too little volatile oil to undergo expression and their chemical components are too delicate and easily denatured by the high heat used in steam distillation. Instead, a solvent such as hexane or supercritical carbon dioxide is used to extract the oils. Extracts from hexane and other hydrophobic solvent are called concretes, which are a mixture of essential oil, waxes, resins, and other lipophilic plant material.
Although highly fragrant, concretes contain large quantities of non-fragrant waxes and resins. As such another solvent, often ethyl alcohol, which only dissolves the fragrant low-molecular weight compounds, is used to extract the fragrant oil from the concrete. The alcohol is removed by a second distillation, leaving behind the absolute.
Supercritical carbon dioxide is used as a solvent in supercritical fluid extraction. This method has many benefits, including avoiding petrochemical residues in the product and the loss of some "top notes" when steam distillation is used. It does not yield an absolute directly. The supercritical carbon dioxide will extract both the waxes and the essential oils that make up the concrete. Subsequent processing with liquid carbon dioxide, achieved in the same extractor by merely lowering the extraction temperature, will separate the waxes from the essential oils. This lower temperature process prevents the decomposition and denaturing of compounds. When the extraction is complete, the pressure is reduced to ambient and the carbon dioxide reverts back to a gas, leaving no residue. An animated presentation describing the process is available for viewing.
Supercritical carbon dioxide is also used for making decaffeinated coffee. However, although it uses the same basic principles it is a different process because of the difference in scale.
Highly faguent plant examples:
