Natural product

A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients.
Within the field of organic chemistry, the definition of natural products is usually restricted to organic compounds isolated from natural sources that are produced by the pathways of primary or secondary metabolism. Within the field of medicinal chemistry, the definition is often further restricted to secondary metabolites. Secondary metabolites are not essential for survival, but nevertheless provide organisms that produce them an evolutionary advantage. Many secondary metabolites are cytotoxic and have been selected and optimized through evolution for use as "chemical warfare" agents against prey, predators, and competing organisms. Secondary or specialized metabolites are often unique to specific species, whereas primary metabolites are commonly found across multiple kingdoms. Secondary metabolites are marked by chemical complexity which is why they are of such interest to chemists.
Natural sources may lead to basic research on potential bioactive components for commercial development as lead compounds in drug discovery. Although natural products have inspired numerous drugs, drug development from natural sources has received declining attention in the 21st century by pharmaceutical companies, partly due to unreliable access and supply, intellectual property, cost, and profit concerns, seasonal or environmental variability of composition, and loss of sources due to rising extinction rates. Despite this, natural products and their derivatives still accounted for about 10% of new drug approvals between 2017 and 2019.

Classes

The broadest definition of natural product is anything that is produced by life, and includes the likes of biotic materials, bio-based materials, bodily fluids, and other natural materials.
Natural products may be classified according to their biological function, biosynthetic pathway, or source. Depending on the sources, the number of known natural product molecules ranges between 300,000 and 400,000.

Function

Following Albrecht Kossel's original proposal in 1891, natural products are often divided into two major classes, the primary and secondary metabolites. Primary metabolites have an intrinsic function that is essential to the survival of the organism that produces them. Secondary metabolites in contrast have an extrinsic function that mainly affects other organisms. Secondary metabolites are not essential to survival but do increase the competitiveness of the organism within its environment. For instance, alkaloids like morphine and nicotine act as defense chemicals against herbivores, while flavonoids attract pollinators, and terpenes such as menthol serve to repel insects. Because of their ability to modulate biochemical and signal transduction pathways, some secondary metabolites have useful medicinal properties.
Natural products especially within the field of organic chemistry are often defined as primary and secondary metabolites. A more restrictive definition limiting natural products to secondary metabolites is commonly used within the fields of medicinal chemistry and pharmacognosy.

Primary metabolites

Primary metabolites, as defined by Kossel, are essential components of basic metabolic pathways required for life. They are associated with fundamental cellular functions such as nutrient assimilation, energy production, and growth and development. These metabolites have a wide distribution across many phyla and often span more than one kingdom. Primary metabolites include the basic building blocks of life: carbohydrates, lipids, amino acids, and nucleic acids.
Primary metabolites involved in energy production include enzymes essential for respiratory and photosynthetic processes. These enzymes are composed of amino acids and often require non-peptidic cofactors for proper function. The basic structures of cells and organisms are also built from primary metabolites, including components such as cell membranes, cell walls, and cytoskeletons.
Enzymatic cofactors that are primary metabolites include several members of the vitamin B family. For instance, vitamin B₁, synthesized from 1-deoxy-D-xylulose 5-phosphate, serves as a coenzyme for enzymes such as pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, and transketolase—all involved in carbohydrate metabolism. Vitamin B₂, derived from ribulose 5-phosphate and guanosine triphosphate, is a precursor to FMN and FAD, which are crucial for various redox reactions. Vitamin B₃, synthesized from tryptophan, is an essential part of the coenzymes NAD and NADP, necessary for electron transport in the Krebs cycle, oxidative phosphorylation, and other redox processes. Vitamin B₅, derived from α,β-dihydroxyisovalerate and aspartic acid, is a component of coenzyme A, which plays a vital role in carbohydrate and amino acid metabolism, as well as fatty acid biosynthesis. Vitamin B₆, functions as pyridoxal 5′-phosphate and acts as a cofactor for enzymes, particularly transaminases, involved in amino acid metabolism. Vitamin B₁₂ contains a corrin ring structure, similar to porphyrin, and serves as a coenzyme in fatty acid catabolism and methionine synthesis.
Other primary metabolite vitamins include retinol, synthesized in animals from plant-derived carotenoids via the mevalonate pathway, and ascorbic acid, which is synthesized from glucose in the liver of animals, though not in humans.
DNA and RNA, which store and transmit genetic information, are synthesized from primary metabolites, specifically nucleic acids and carbohydrates.
First messengers are signaling molecules that regulate metabolism and cellular differentiation. These include hormones and growth factors composed of peptides, biogenic amines, steroid hormones, auxins, and gibberellins. These first messengers interact with cellular receptors, which are protein-based, and trigger the activation of second messengers to relay the extracellular signal to intracellular targets. Second messengers often include primary metabolites such as cyclic nucleotides and diacyl glycerol.

Secondary metabolites

Secondary in contrast to primary metabolites are dispensable and not absolutely required for survival. Furthermore, secondary metabolites typically have a narrow species distribution.
Secondary metabolites have a broad range of functions. These include pheromones that act as social signaling molecules with other individuals of the same species, communication molecules that attract and activate symbiotic organisms, agents that solubilize and transport nutrients, and competitive weapons that are used against competitors, prey, and predators. For many other secondary metabolites, the function is unknown. One hypothesis is that they confer a competitive advantage to the organism that produces them. An alternative view is that, in analogy to the immune system, these secondary metabolites have no specific function, but having the machinery in place to produce these diverse chemical structures is important and a few secondary metabolites are therefore produced and selected for.
General structural classes of secondary metabolites include alkaloids, phenylpropanoids, polyketides, and terpenoids.

Biosynthesis

The biosynthetic pathways leading to the major classes of natural products are described below.

Carbohydrates

s are organic molecules essential for energy storage, structural support, and various biological processes in living organisms. They are produced through photosynthesis in plants or gluconeogenesis in animals and can be converted into larger polysaccharides:

Photosynthesis or gluconeogenesis → monosaccharides → polysaccharides

Carbohydrates serve as a primary energy source for most life forms. Additionally, polysaccharides derived from simpler sugars are vital structural components, forming the cell walls of bacteria and plants.
During photosynthesis, plants initially produce, a three-carbon triose. This can be converted into glucose or various pentoses through the Calvin cycle. In animals, three-carbon precursors like lactate or glycerol are converted into pyruvate, which can then be synthesized into carbohydrates in the liver.

Fatty acids and polyketides

s and polyketides are synthesized via the acetate pathway, which starts from basic building blocks derived from sugars:

Sugars → acetate pathway → fatty acids and polyketides

During glycolysis, sugars are broken down into acetyl-CoA. In an ATP-dependent enzymatic reaction, acetyl-CoA is carboxylated to form malonyl-CoA. Acetyl-CoA and malonyl-CoA then undergo a Claisen condensation, releasing carbon dioxide to form acetoacetyl-CoA which is used by the mevalonate pathway to produce steroids. In fatty acid synthesis, one molecule of acetyl-CoA and several molecules of malonyl-CoA are condensed by fatty acid synthase. After each round of elongation, the keto group is reduced, the intermediate alcohol dehydrated, and resulting enoyl-CoAs are reduced to acyl-CoAs. Fatty acids are essential components of lipid bilayers that form cell membranes and serve as energy storage in the form of fat in animals.
The plant-derived fatty acid linoleic acid is converted in animals through elongation and desaturation into arachidonic acid, which is then transformed into various eicosanoids, including leukotrienes, prostaglandins, and thromboxanes. These eicosanoids act as signaling molecules, playing key roles in inflammation and immune responses.
Alternatively the intermediates from additional condensation reactions are left unreduced to generate poly-β-keto chains, which are subsequently converted into various polyketides. The polyketide class of natural products has diverse structures and functions and includes important compounds such as macrolide antibiotics.