Natural product

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A natural product is a chemical compound or substance produced by a living organism - found in nature. In a broad sense, natural products include whatever substances life produces. Natural products can also be prepared with chemical synthesis (both semisynthesis and total synthesis) and have played a central role in the development of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without adding artificial ingredients.

In the field of organic chemistry, the definition of natural products is usually limited to pure organic compounds isolated from natural sources produced by primary or secondary metabolic pathways. In the field of medical chemistry, the definition is often more limited to secondary metabolites. Secondary metabolism is not essential to survival, but nevertheless provides organisms that produce them an evolutionary advantage. Many secondary metabolites are cytotoxic and have been selected and optimized through evolution to be used as agents of "chemical warfare" against prey, predators, and competing organisms.

Natural products sometimes have therapeutic benefits as traditional remedies for treating diseases, producing knowledge to obtain active components as lead compounds for drug discovery. Although natural products have inspired many of the drugs approved by the US Food and Drug Administration, the development of medicines from natural sources has been receiving a dwindling attention by pharmaceutical companies, in part because of unreliable access and supply, concerns about intellectual property, seasonal or environmental variability, and loss of resources as extinction rates increase.

Video Natural product

Class

The broad definition of natural products is anything that life produces, and includes materials such as biota (eg wood, silk), bio-based materials (eg bioplastics, cornstarch), body fluids (eg milk, plant exudates), and other natural materials (eg soil, coal). A stricter definition of a natural product is an organic compound synthesized by living organisms. The rest of this article confines itself to this narrower definition.

Natural products can be classified according to their biological functions, biosynthetic pathways, or sources as described below.

Maps Natural product

Function

Following the original proposal of Albrecht Kossel in 1891, natural products are often divided into two main classes, namely primary and secondary metabolites. Primary metabolites have intrinsic functions that are essential for the survival of the organisms that produce them. Different secondary metabolism has extrinsic functions that primarily affect other organisms. Secondary metabolism is not essential for survival but enhances the competitiveness of organisms in the environment. Because of their ability to modulate biochemical and signal transduction pathways, some secondary metabolites have beneficial medicinal properties.

Natural products especially in the field of organic chemistry are often defined as primary and secondary metabolites. A more limiting definition limiting natural products to secondary metabolites is commonly used in the fields of medical chemistry and pharmacogniosis.

Main metabolite

The primary metabolite as defined by Kossel is the basic metabolic pathway component necessary for life. They are associated with important cellular functions such as assimilation of nutrients, energy production, and growth/development. They have a wide distribution of species that includes many phyla and often more than one kingdom. Major metabolisms include carbohydrates, lipids, amino acids, and nucleic acids which are the basic building blocks of life.

Major metabolites involved with energy production include respiratory enzymes and photosynthesis. Enzymes in turn consist of amino acids and often non-peptidic cofactors which are essential for enzyme function. The basic structure of cells and organisms also comprises primary metabolites. These include cell membranes (eg phospholipids), cell walls (eg peptidoglycan, chitin), and cytoskelet (protein).

The primary enzymatic cofactors of primary metabolites include family members of vitamin B. Vitamin B1 as thiamine diphosphate is a coenzyme for pyruvic dehydrogenase, 2-oxoglutarate dehydrogenase, and transcetolase all of which are involved in carbohydrate metabolism. Vitamin B2 (riboflavin) is the FMN and FAD constituent required for many redox reactions. Vitamin B3 (nicotinic acid or niacin), synthesized from tryptophan is a coenzyme component of NAD and NADP which in turn is necessary for electron transport in the Krebs cycle, oxidative phosphorylation, as well as many redox reactions others. Vitamin B5 (pantothenic acid) is a coenzyme A constituent, the basic component of carbohydrate and amino acid metabolism as well as the biosynthesis of fatty acids and polyketides. Vitamin B6 (pyridoxol, pyridoxal, and pyridoxamine) as pyridoxal 5? -phosphate is a cofactor for many enzymes, especially transaminases involved in amino acid metabolism. Vitamin B12 (cobalamins) contains a similar corrin ring in the structure for porphyrin and is an important coenzyme for fatty acid catabolism as well for methionine biosynthesis.

DNA and RNA that store and transmit genetic information consists of primary metabolites of nucleic acids.

The first messenger signifies molecules that control metabolism or cellular differentiation. These signaling molecules include hormones and growth factors in turn composed of peptides, biogenic amines, steroid hormones, auxins, gibberellins etc. This first debt interacts with cell receptors composed of proteins. The cellular receptors in turn activate the second messenger used to deliver extracellular messages to intracellular targets. These signal molecules include the main cyclic nucleotide metabolites, diacylglycerol etc.

Secondary metabolism

Secondary is different from primary metabolites that are discarded and not absolutely necessary to survive. Furthermore, secondary metabolites usually have a narrow species distribution.

Secondary metabolism has many functions. These include pheromones that act as social signaling molecules with other individuals of the same species, attractive communication molecules and activate symbiotic organisms, agents that dissolve and transport nutrients (siderophores etc.), and competitive weapons (repellants, venoms, toxins, etc.). ) used against competitors, prey, and predators. For many other secondary metabolites, the function is unknown. One hypothesis is that they provide a competitive advantage to the organism that produces it. An alternative view is that, in the analogy of the immune system, this secondary metabolite has no specific function, but having a machine in place to produce this diverse chemical structure is important and some secondary metabolites are therefore produced and selected.

Common structural classes of secondary metabolites include alkaloids, phenylpropanoids, polybutics, and terpenoids, which are described in more detail in the biosynthetic section below.

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Biosynthesis

Biosynthetic pathways leading to the main classes of natural products are described below.

• Photosynthesis or gluconeogenesis -> monosaccharides -> polysaccharides (cellulose, chitin, glycogen etc.)
• Acetate strips -> fatty acids and polybutics
• Shikimate Path -> aromatic amino acids and phenylpropanoid
• Mevalonate pathways and methyletrythritol phosphate pathways -> terpenoids and steroids
• Amino acids -> alkaloids

Carbohydrates

Carbohydrates are an important source of energy for most forms of life. In addition, polysaccharides formed from simpler carbohydrates are important structural components of many organisms such as bacterial and plant cell walls.

Carbohydrates are the result of photosynthesis of plants and animal gluconeogenesis. Photosynthesis produces initially 3-phosphoglyceraldehyde, three carbon atoms containing sugar (triose). This triose can in turn be converted into glucose (six carbon atoms containing sugar) or various pentoses (five carbon atoms containing sugar) through the Calvin cycle. In animals, three precursors of lactated carbon or glycerol can be converted into pyruvate which in turn can be converted into carbohydrates in the liver.

Fatty acids and polyketides

Through the process of sugar glycolysis is broken down into acetyl-CoA. In an enzymatic catalyzed ATP reaction, acetyl-CoA is oxidized to form malonyl-CoA. Acetyl-CoA and malonyl-CoA undergo Claisen condensation with carbon dioxide loss to form acetoacetyl-CoA. Additional condensation reactions produce a higher molecular weight poly-io-keto chain which is then converted to other polymers. The natural product polyketide class has a variety of structures and functions and includes prostaglandins and macrolide antibiotics.

One acetyl-CoA molecule ("starter unit") and some malonyl-CoA molecules ("unit extender") are condensed by fatty acid synthase to produce fatty acids. Fatty acids are an important component of lipid bilayers that make up cell membranes as well as storage of fat energy in animals.

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Source

Natural products can be extracted from cells, tissues, and secretions of microorganisms, plants and animals. The unfractionated extract from one of these sources will contain a variety of structurally diverse and often newly structured compounds. Chemical diversity in nature is based on biodiversity, so researchers travel around the world to get samples for analysis and evaluation on drug discovery screens or bioassays. This effort to look for natural products is known as bioprospecting.

Pharmacognotics provides a means to identify, select and process natural products intended for drug use. Normally, natural product compounds have some form of biological activity and they are known as active principles - such structures can evolve into the discovery of "lead". In this way and related ways, some drugs are currently obtained directly from natural sources.

On the other hand, some drugs are developed from natural products originally obtained from natural sources. This means the instructions may be:

• is generated by total synthesis, or
• the starting point (precursor) for semisynthetic compounds, or
• the framework that serves as the basis for the different compounds structurally arrives with total/semisynthesis.

This is because many biologically active natural products are secondary metabolites often with complex chemical structures. This has the advantage because they are new compounds but this complexity also complicates the synthesis of such compounds; otherwise the compound may need to be extracted from natural sources - slow, expensive and inefficient processes. As a result, there is usually an advantage in designing a simpler analogue.

Prokaryotic

Bacteria

The coincidental discovery and subsequent clinical success of penicillin encourage large-scale search for other environmental microorganisms that may produce natural anti-infectious products. Soil and water samples are collected from around the world, leading to the discovery of streptomycin (derived from Streptomyces griseus ), and the awareness that bacteria, not just fungi, are an important source of natural active pharmacology. product. This, in turn, leads to the development of the impressive weaponry of antibacterial and antifungal agents including amphotericin B, chloramphenicol, daptomycin and tetracycline (from Streptomyces spp.), Polymyxins (from Paenibacillus polymyxa >), and rifamycins (from Amycolatopsis rifamycinica ).

Although most of the drugs that come from bacteria are used as anti-infections, some have been found used in other medical fields. Botulinum toxins (from Clostridium botulinum ) and bleomycin (from Streptomyces verticillus ) are two examples. Botulinum, a neurotoxin responsible for botulism, can be injected into certain muscles (such as those that control the eyelid) to prevent muscle spasms. Also, bleomycin glycopeptide is used for the treatment of several cancers including Hodgkin's lymphoma, head and neck cancer, and testicular cancer. New trends in the field include metabolic profiles and isolation of natural products from new bacterial species present in unexplored environments. Examples include symbionts or endophytes from tropical environments, underground bacteria found underground through mining/drilling, and marine bacteria.

Archaea

Since many Archaea have adapted to life in extreme environments such as polar regions, thermal springs, acid springs, alkaline springs, salt lakes, and deep seawater pressures, they have enzymes that function under unusual conditions. This enzyme is a potential use in the food, chemical and pharmaceutical industries, where biotechnological processes often involve high temperatures, extreme pH, high salt concentrations, and/or high pressure. Examples of enzymes identified to date include amylase, pullulanase, cyclodextrin glycosyltransferase, cellulase, xylanase, chitinase, protease, alcohol dehydrogenase, and esterase. Archaea is the source of new chemical compounds as well, for example isoprenyl glycerol ether 1 and 2 of Thermococcus S557 and Methanocaldococcus jannaschii , respectively.

Eukaryotic

Mushroom

Some anti-infective drugs have been derived from fungi including penicillin and cephalosporins (antibacterial drugs from Penicillium chrysogenum and Cephalosporium acremonium respectively) and griseofulvin (antifungal drugs from > Penicillium griseofulvum ). Other medically useful medicinal metabolites include lovastatin (from Pleurotus ostreatus ), which is the cause for a series of drugs that lower cholesterol, cyclosporin (from Tolypocladium inflatum), which is used for suppress the immune response after organ transplant surgery, and ergometrine (from Claviceps spp.), which acts as a vasoconstrictor, and is used to prevent bleeding after childbirth. Asperlicin (from Aspergillus alliaceus ) is another example. Asperlicin is a new antagonist of cholecystokinin, a neurotransmitter suspected of involvement in panic attacks, and potentially used to treat anxiety.

Plants

Plants are the main source of complex and highly structurally complex chemical compounds (phytochemicals), this structural diversity is due in part to the natural selection of organisms that produce potent compounds to prevent herbivores (feeding deterrents). The main classes of phytochemicals include phenols, polyphenols, tannins, terpenes, and alkaloids. Although the number of plants that have been studied extensively is relatively small, many pharmacologically active natural products have been identified. Useful clinical examples include paclitaxel anticancer agents and omacetaxine mepesuccinate (from Taxus brevifolia and Cephalotaxus harringtonii , respectively), artemisinin antimalarial agents (from Artemisia annua ), and the acetylcholinesterase galantamine inhibitor (from Galanthus spp.), is used to treat Alzheimer's disease. Medicines derived from other plants, used as medicines and/or recreations include morphine, cocaine, quinine, tubocurarin, muscarin and nicotine.

Animal

Animals are also a source of bioactive natural products. In particular, venomous animals such as snakes, spiders, scorpions, caterpillars, bees, wasps, centipedes, ants, frogs and frogs have attracted much attention. This is because the toxic constituents (peptides, enzymes, nucleotides, lipids, biogenic amines, etc.) often have very specific interactions with macromolecule targets in the body (eg? -bungarotoxin from cobra). As with plant-prevention, this biological activity is associated with natural selection, organisms capable of killing or paralyzing their prey and/or defending themselves against predators who are more likely to survive and reproduce.

Because of the interaction of these specific chemical targets, toxic constituents have been shown to be important tools for studying receptors, ion channels, and enzymes. In some cases, they also serve as leaders in the development of new drugs. For example, teprotide, a peptide isolated from the Brazil viper pit Bothrops jararaca , is an indication of the development of antihypertensive agents of cilazapril and captopril. Also, echistatin, the disintegrin of the venomous snake venom Echis carinatus is a clue in the development of antiplatelet ointment.

In addition to the above ground and amphibian animals, many marine animals have been examined for pharmacologically active natural products, with corals, sponges, tunicates, sea slugs and bryozoans producing chemicals with intense analgesic, antiviral, and anticancer activity. Two examples developed for clinical use include? -conotoxin (from sea slugs Conus magus ) and ecteinascidin 743 (from tunicate Ecteinascidia turbinata ). The first,? -conotoxin, is used to relieve severe and chronic pain, while the latter, ecteinascidin 743 is used to treat metastatic soft tissue sarcomas. Other natural products derived from marine animals and under investigation may include therapeutic agents including discodermolide antitumor agents (from spongy discodermia dissoluta), eleutherobin (from coral Erythropodium caribaeorum ), and bryostatins (from bryozoan Bugula neritina ).

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Medical use

Natural products sometimes have pharmacological activities that can be useful therapeutic in treating diseases. Thus, natural products are an active component of many traditional medicines. Furthermore, synthetic analogs of natural products with enhanced potency and safety can be prepared and therefore natural products are often used as a starting point for drug discovery. Natural product constituents have inspired many drug discovery efforts that finally got approval as new drugs by the US Food and Drug Administration

Traditional medicine

Indigenous peoples and ancient civilizations experimented with different parts of plants and animals to determine what effect they might have. Through trial and error in isolated cases, traditional healers or shamans find some sources to provide a therapeutic effect, representing knowledge of inherited medicines passed down through generations in practices such as traditional Chinese medicine and Ayurveda. Extracts of some natural products led to the modern invention of their active ingredients and finally on the development of new drugs.

Natural remedies derived from natural products

A large number of prescribed drugs today are derived from or inspired by natural products. Some representative examples are listed below.

Some of the oldest natural-based drug-based products are analgesics. The bark of willow trees has been known since antiquity to have a painkilling properties. This is due to the natural salicin product which in turn can be hydrolyzed to salicylic acid. The acetylsalicylic acid synthetic derivative better known as aspirin is a widely used pain reliever. The mechanism of action is the inhibition of the enzyme cyclooxygenase (COX). Another important example is that opium is extracted from latex from Papaver somniferous (flowering poppy plant). The most powerful narcotic component of opium is an alkaloid morphine that acts as an opioid receptor agonist. A more recent example is the blocking of the N-type ziconotide analgesic-type calcium channel based on conic peptide cone cyclic (? -conotoxin MVIIA) of the species conus magus .

A large number of anti-infections are based on natural products. The first antibiotic found, penicillin, was isolated from the Penicillium mold. Penicillin and associated beta-lactam work by inhibiting the enzyme DD-transpeptidase required by bacteria to cross the peptidoglycan into the cell wall.

Some natural product drugs target tubulin, which is a component of the cytoskeleton. These include tubulin colchicine polymerization inhibitors isolated from Colchicum autumnale (the autumn crocus flowering plant), which is used to treat gout. Colchicine is synthesized from the amino acids phenylalanine and tryptophan. Paclitaxel, on the other hand, is a tubulin polymerisation stabilizer and is used as a chemotherapy drug. Paclitaxel is based on a taxol of terpenoid natural products, isolated from Taxus brevifolia (yew pacific tree).

A class of drugs widely used to lower cholesterol is the HMG-CoA reductase inhibitor, eg atorvastatin. It was developed from mevastatin, a polyketide produced by the fungus Penicillium citrinum . Finally, a number of natural product drugs are used to treat hypertension and congestive heart failure. These include angiotensin captopril inhibitor inhibitors. Captopril is based on a potential factor of peptidic bradycinin isolated from Viper's poison snake ( Bothrops jararaca ).

Limiting factor and enabling

Many challenges limit the use of natural products for drug discovery, which result in 21st century preferences by pharmaceutical companies to dedicate discovery efforts toward high throughput screening of purely synthetic compounds with shorter timelines for refinement. Natural product sources are often unreliable to access and supply, have high probability of duplication, inherently create intellectual property concerns about patent protection, vary in composition due to source or environmental seasons, and are vulnerable to increased extinction rates.

Biological resources for drug discovery of natural products remain abundant, with a small percentage of microorganisms, plant species, and insects assessed for bioactivity. In very large numbers, bacteria and marine microorganisms remain untested. In 2008, the metagenomic field was proposed to test the genes and their functions in soil microbes, but most pharmaceutical companies did not exploit these resources completely, instead choosing to develop "diversity-oriented syntheses" from libraries of known drugs or natural sources for lead compounds with higher bioactivity potential.

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Isolation and purification

All natural products are started as a mixture with other compounds from natural sources, often very complex mixtures, from which attractive products must be isolated and purified. The insulation of natural products refers, depending on the context, both for the isolation of sufficient quantities of pure chemicals for the elucidation of chemical structures, chemical derivation/degradation, biological testing, and other research needs (generally milligrams for grams, but historically, often more), or the isolation of "analytic quantities" of interesting substances, where the focus is on the identification and quantization of substances (eg in biological or fluid tissue), and where the isolated amount depends on the applied analytical method but generally always sub-microgram scale). The ease with which the active agent can be isolated and purified depends on the structure, stability, and quantity of natural products. The isolation methods applied to achieve two different product scales are also different, but generally involve extraction, precipitation, adsorption, chromatography, and sometimes crystallization. In both cases, the isolated substance is purified into chemical homogeneity , ie the separation of certain combinations and analytical methods such as the LC-MS method selected to be "orthogonal" - achieving their separation based on different modes of interaction between substance and isolate the matrix - with the aim of repeating the detection of only one species present in a putative pure sample. Initial isolation is almost certainly followed by structural determination, especially if important pharmacological activity is associated with purified natural products.

Structural determination refers to the method applied to determine the chemical structure of an isolated, pure natural product, a process involving a series of chemical and physical methods that have changed significantly during the history of natural product research; in the early days, it focused on the chemical transformation of unknown substances into known substances, and measurement of physical properties such as melting and boiling points, and related methods for determining molecular weight. In the modern era, methods focus on mass spectrometry and nuclear magnetic resonance methods, often multidimensional, and, where possible, small molecular crystallography. For example, the chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in 1945, a job which he later received the Nobel Prize in Chemistry (1964).

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Synthesis

Many natural products have very complex structures. The perceived complexity of a natural product is a qualitative problem, comprising the consideration of its molecular mass, the arrangement of a particular substructure (functional groups, rings, etc.) Taking into account each other, the number and density of the functional groups, their stability. of the groups and molecules as a whole, the number and types of stereochemical elements, the physical properties of the molecules and their intermediates (which bear on their ease of handling and purification), are all seen in the context of the novelty of the structure and whether previous synthetic attempts have been successful (see below for details). Some natural, especially less complex, easy and cost-effective products are made through complete chemical synthesis of simpler and simpler chemicals, a process called total synthesis (especially when the process does not involve a step that is mediated by biological agents). Not all natural products agree with total synthesis, cost-effective or otherwise. In particular, the most complex is often not. Many are accessible, but the necessary route is too expensive to allow synthesis on a practical or industrial scale. However, in order to be available for further study, all natural products should result in isolation and purification. This may be sufficient if the insulation provides the appropriate amount of natural products for the intended purpose (eg as a medicine to relieve the disease). Drugs such as penicillin, morphine, and paclitaxel have been shown to be advantageously obtained at the commercial scale required solely through isolation procedures (without significant synthetic chemical contributions). However, in other cases, the required agent is not available without synthetic chemical manipulation.

Semisintesis

The process of isolating natural products from their sources can be costly in terms of time and material costs, and may challenge the availability of dependable natural resources (or have ecological consequences for resources). For example, it has been estimated that the bark of the whole yew tree ( Taxus brevifolia ) should be harvested to extract enough paclitaxel with just one dose of therapy. Furthermore, the amount of structural analogs that can be obtained for activity-structure analysis (SAR) only through harvest (if more than one structural analogue even exists) is limited by the biology of the workplace in the organism, and so outside experimental control.

In such cases where the final target is more difficult to obtain, or limiting the SAR, it is sometimes possible to look for the initial or final stage of the biosynthesis or analogue preview from which the final target can be prepared. This is called semisynthesis or partial synthesis . With this approach, the associated biosynthetic intermediates are harvested and then converted into final products by conventional chemical synthesis procedures.

This strategy can have two advantages. First, the intermediate may be more easily extracted, and in higher yield, than the final desired product. An example of this is paclitaxel, which can be produced by extracting 10-deacetylbaccatin III from T. brevifolia needles, then performing a four-step synthesis. Second, the designed route between the semisynthetic starting materials and the final product can allow analogues of the final product to be synthesized. New generation semisynthetic penicillin is an illustration of the benefits of this approach.

Total synthesis

In general, the total synthesis of natural products is a non-commercial research activity, aimed at a more in-depth understanding of the synthesis of a particular natural product framework, and the development of a new, synthetic method that is fundamental. Nevertheless, it is of tremendous commercial and civic importance. By providing a challenging synthetic target, for example, he has played a central role in the development of organic chemistry. Prior to the development of analytical chemistry methods in the 20th century, natural product structures were confirmed by total synthesis (so-called "structure of evidence by synthesis"). Initial efforts in the synthesis of natural products target complex substances such as cobalamin (vitamin B ₁₂ ), an important cofactor in cellular metabolism.

Symmetry

The examination of naturally dimerized and trimerized products has shown that elements of bilateral symmetry are often present. Bilateral symmetry refers to a molecule or system that contains the identity of a group of points C ₂ , C _s , or C _2v . C ₂ symmetry tends to be much more than other types of bilateral symmetry. These findings explain how these compounds can be made mechanically, and provide insight into the thermodynamic properties that make these compounds more advantageous. The theoretical functional density (DFT), Hartree Fock, and semiempirical calculations also show some favorability for dimerization in natural products due to the evolution of more energy per bond than equivalent trimers or tetramer. This is proposed because of steric barriers in the molecular core, as most natural products dimerize and trimerize in head-to-head mode rather than head-to-tail.

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Research and teaching

Research and teaching activities related to natural products fall into a number of different academic fields, including organic chemistry, medical chemistry, pharmacognism, ethnobotany, traditional medicine and ethnopharmacology. Other biological areas include chemical biology, chemical ecology, chemogenomics, and system biology.

Chemistry

Chemical natural products are different fields of important chemical research in the history of chemistry, the source of substances in early preclinical drug discovery research, the understanding of traditional medicine and ethnopharmacology, the evolution of technologies related to chemical separation, the development of modern methods in the determination of chemical structures by NMR and techniques and in the identification of pharmacologically beneficial areas of the chemical diversity space. In addition, natural products are prepared by organic synthesis, and have played a central role for the development of organic chemistry by providing challenging targets and problems for synthetic strategies and tactics. In this case, natural products play a central role in the training of new synthetic organic chemistry, and are a major motivation in the development of new variants of old chemical reactions (eg, Evans aldol reaction), as well as the invention of new chemical reactions (eg Woodward cis-hydroxylation, Sharpless epoxidation, and Suzuki-Miyaura cross-coupling reaction).

Biochemistry

Research is underway to understand and manipulate the biochemical pathways involved in the synthesis of natural products in plants. It is expected that this knowledge will enable medically beneficial phytochemicals such as alkaloids to be produced more efficiently and economically.

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History

Organic and natural product chemical foundation

The concept of natural products dates back to the early 19th century, when the basics of organic chemistry were laid. Organic chemistry was considered at that time as a chemical substance consisting of plants and animals. It is a relatively complex chemical form and stands in stark contrast to inorganic chemistry, the principles laid down in 1789 by the Frenchman Antoine Lavoisier in his work Traità © ÃÆ'â € ° lÃÆ' © mentaire de Chimie .

Isolation

Lavoisier pointed out at the end of the 18th century that organic matter consists of a number of elements: mainly carbon and hydrogen and coupled with oxygen and nitrogen. He went quickly to focus on the isolation of these substances, often because they had interesting pharmacological activities. Plants are the main source of such compounds, especially alkaloids and glycosides. It has long been known that opium, a sticky alkaloid mixture (including codeine, morphine, noscapin, thebaine, and papaverine) of opium poppy (Papaver somniferum), has a narcotic and at the same time changes the nature of the mind. Already in 1805 was morphine isolated by German chemist Friedrich SertÃÆ'¼rner and in the 1870s it was found that boiling morphine with acetic anhydride produced a substance with a strong pain-suppressing effect: heroin. In 1815, EugÃÆ'¨ne Chevreul was isolated from animal tissue cholesterol, a steroid-type crystalline substance, and in 1820 was strychnine, an alkaloid isolated.

Synthesis

The second important step is the synthesis of organic compounds. While the synthesis of inorganic substances has been known for a long time, the synthesis of organic substances is a difficult obstacle. In 1827, Swedish chemist JÃÆ'¶ns Jacob Berzelius argued that an indispensable natural force for the synthesis of organic compounds, called vital forces or life forces, is required. This philosophical idea, vitalism, until the nineteenth century had many supporters, even after the introduction of atomic theory. The idea of ​​vitalism is particularly compatible with belief in medicine; most traditional healing practices believe that disease is the result of some imbalances in vital energies that distinguish life from non-living. The first attempt to solve the idea of ​​vitalism in science was made in 1828, when German chemist Friedrich WÃÆ'¶hler succeeded in synthesizing urea, a natural product found in urine, by heating ammonium cyanate, an inorganic substance:

${\ displaystyle \ mathrm {NH_ {4} OCN \ {\ xrightarrow {\ \ 60 \ {\ circ} C \ \}} \ H_ {2} NCONH_ {2}}}$

This reaction shows that there is no need for life force to prepare organic substances. This idea, however, initially met with high levels of skepticism, and only 20 years later, with the synthesis of acetic acid from carbon by Adolph Wilhelm Hermann Kolbe, was an accepted idea. Organic chemistry has since developed into an independent area of ​​research dedicated to the study of carbonaceous compounds, since the same element is detected in a variety of substances derived from nature. An important factor in the characterization of organic matter is based on their physical properties (such as melting point, boiling point, solubility, crystallinity, or color).

Structural theory

The third step is the structure of the explanation of organic matter: although the composition of elements of pure organic matter (regardless of whether they come from nature or synthetics) can be determined fairly accurately, the molecular structure is still a problem. The drive for structural elucidation results from a dispute between Friedrich WÃÆ'¶hler and Justus von Liebig, both of whom study silver salts of the same composition but have different properties. WÃÆ'¶hler studied silver cyanates, a harmless substance, while von Liebig investigated the fulminate silver, salt with explosive properties. The elemental analysis shows that both salts contain equal amounts of silver, carbon, oxygen and nitrogen. According to the prevailing ideas, the two substances must have the same properties, but this is not the case. This apparent contradiction is then solved by the theory of Berzelius isomers, in which not only quantities and types of elements are important for chemical properties and reactivity, but also the position of atoms in a compound. This is a direct cause for the development of structural theory, such as the radical theory of Jean-Baptiste Dumas and the substitution theory of Auguste Laurent. However, until 1858 before August KekulÃÆ'Â| formulated a definite structure theory. He suggests that carbon tetravalent ads can bind themselves to carbon chains when they occur in natural products.

Extending the concept

The concept of a natural product, originally based on organic compounds that can be isolated from plants, expanded to include animal material in the mid-19th century by Justus von Liebig of Germany. Hermann Emil Fischer in 1884, turned his attention to the study of carbohydrates and purines, a job he was awarded the Nobel Prize in 1902. He also succeeded in synthesizing labs in various carbohydrates, including glucose and mannose. After the discovery of penicillin by Alexander Fleming in 1928, fungi and other micro-organisms were added to the warehouse of natural product sources.

Milestones

In the 1930s, some great classes of natural products are known. Important milestones include:

• Terpenes, was first studied systematically by Otto Wallach (Nobel Prize 1910) and later by Leopold Ru? i? ka (Nobel Prize in 1939)
• Porfin-based dyes (including chlorophyll and heme), were studied by Richard WillstÃÆ'¤tter (Nobel Prize 1915) and Hans Fischer (Nobel Prize 1930)
• Steroids, studied by Heinrich Otto Wieland (Nobel Prize in 1927) and Adolf Windaus (Nobel Prize in 1928)
• Carotenoid, studied by Paul Karrer (Nobel Prize 1937)
• Vitamin, studied among others by Paul Karrer, Adolf Windaus, Robert R. Williams, Norman Haworth (Nobel Prize in 1937), Richard Kuhn (Nobel Prize in 1938) and Albert Szent-GyÃÆ'¶rgyi
• The hormones were studied by Adolf Butenandt (Nobel Prize in 1939) and Edward Calvin Kendall (Nobel Prize 1950)
• Alkaloid and anthocyanin, studied by, among others, Robert Robinson (Nobel Prize 1947)

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Also see

• Appeal to nature
• Ethnobotany
• Farmacognition
• Phytotherapy
• Secondary metabolism

Journal

• Natural Chemical Compounds
• Natural Product Journal
• Natural Product Report
• Natural Product Research

Reference

Further reading

External links

• Reusch W (2010). "Natural Product Page". Organic Chemistry Virtual Text . Ann Arbor, Mich: Michigan State University, Department of Chemistry. Archived from the original on February 3, 2007.
"NAPROC-13 Basis data de Carbono 13 de Productos Naturales y Relacionados ( Carbon-13 Database of Natural Products and Related Substances )". Spanish tool for facilitating structural identification of natural products.
• Porter N, ed. (1913). "Natural products". Webster Dictionary . Springfield, Massachusetts: C. & amp; G. Merriam Co.

Source of the article : Wikipedia