Barbatic acid is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...

that is made by some lichens. It is in the structural class known as depsides. It is particularly common in the genera ''

Usnea ''Usnea'' is a genus of mostly pale grayish-green fruticose lichens that grow like leafless mini-shrubs or tassels anchored on bark or twigs.Field Guide to California Lichens, Stephen Sharnoff, Yale University Press, 2014, The genus is in the f ...

'' (the beard lichens) and ''

Cladonia ''Cladonia'' is a genus of moss-like lichens in the family Cladoniaceae. They are the primary food source for reindeer/caribou. ''Cladonia'' species are of economic importance to reindeer-herders, such as the Sami in Scandinavia or the Nenets ...

''.

History

The compound was first isolated in 1880 from the lichen '' Usnea barbata'' by chemists

John Stenhouse John Stenhouse FRS FRSE FIC FCS (21 October 1809 – 31 December 1880) was a Scottish chemist. In 1854, he invented one of the first practical respirators. He was a co-founder of the Chemical Society in 1841. Life John Stenhouse was born ...

and Charles Groves. The compound coccellic acid, isolated from '' Cladonia coccifera'', was later shown to be the same compound as barbatic acid.

Properties

Biosynthetically, barbatic acid is made of two units of orsellinate derivatives that are created by an aromatic synthase

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

. The repeated action of this enzyme produces an 8-carbon

polyketide Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

intermediate that is cyclized. Barbatic acid's

IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...

name is 2-hydroxy-4-(2-hydroxy-4-methoxy-3,6-dimethylbenzoyl)oxy-3,6-dimethylbenzoic acid. Its

chemical formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbol ...

is C₁₉H₂₀O₇; it has a

molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...

of 360.36 grams per mole. In its purified crystalline form, it exists as various forms: small rhombic prisms, long needles, or delicate thin sheets (

lamellae Lamella (plural lamellae) means a small plate or flake in Latin, and in English may refer to: Biology * Lamella (mycology), a papery rib beneath a mushroom cap * Lamella (botany) * Lamella (surface anatomy), a plate-like structure in an animal * ...

). Its

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depen ...

is . The

crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric patterns ...

of the

methyl ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

of barbatic acid (i.e., methyl 2-hydroxy-4-(2-hydrocy-4-methoxy-3,6-dimethylbenzoyloxy)-3,6-dimethylbenzoate, or barbatin) has been characterised. It is in the

triclinic crystal system 180px, Triclinic (a ≠ b ≠ c and α ≠ β ≠ γ ) In crystallography, the triclinic (or anorthic) crystal system is one of the 7 crystal systems. A crystal system is described by three basis vectors. In the triclinic system, the crystal i ...

, in the

space group In mathematics, physics and chemistry, a space group is the symmetry group of an object in space, usually in three dimensions. The elements of a space group (its symmetry operations) are the rigid transformations of an object that leave it uncha ...

called P. In this crystal form, two highly substituted

phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...

rings are bridged by an ester group and are inclined towards each other at 106.1°. There are two strong intramolecular hydrogen bonds between the

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydro ...

substituents an the adjacent ester

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...

groups. The crystal structure of pure barbatic acid, determined using single crystal X-ray diffraction analysis, was reported in 2019.

Synthesis

A synthesis for barbatic acid was reported in 1975 using

trifluoroacetic acid Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with ...

as a condensing agent. In 2022, a

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

was reported; the eight-step procedure starts with commercially available methyl atrarate, producing barbatic acid in a 22% total yield. A

high-performance liquid chromatography High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...

(HPLC) technique has been adapted to couple the HPLC output with a photodiode array detector to screen for lichen products based on their specific ultraviolet–visible spectra. In this way, barbatic acid is detected by monitoring its

retention time In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...

, and verifying the presence of three peaks representing wavelengths of maximum absorption (λ_max) at 214, 276, and 310 nm.

Research

Some preliminary research suggests that based on the ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

'' molluscicidal activity of barbatic acid against the human parasite '' Schistosoma mansoni'', it may have potential use in the large-scale control and/or eradication of schistosomiasis. Other research has shown that it is non-toxic to human

peripheral blood mononuclear cell A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus. These cells consist of lymphocytes (T cells, B cells, NK cells) and monocytes, whereas erythrocytes and platelets have no nuclei, and granulocytes ( ...

s at concentrations that are effective against the parasite. Barbatic acid inhibits

photosynthesis Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...

by irreversible binding to the proteins in the photosystem II complex. Immobilised cells of the lichen '' Cladonia miniata'' var. ''parvipes'' have been used to synthesise barbatic acid. The cells were given

sodium acetate Sodium acetate, CH3COONa, also abbreviated Na O Ac, is the sodium salt of acetic acid. This colorless deliquescent salt has a wide range of uses. Applications Biotechnological Sodium acetate is used as the carbon source for culturing bacteria ...

calcium acetate Calcium acetate is a chemical compound which is a calcium salt of acetic acid. It has the formula Ca(C2H3O2)2. Its standard name is calcium acetate, while calcium ethanoate is the systematic name. An older name is acetate of lime. The anhydrous ...

as a

precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...

for

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...

biosynthesis. Laboratory experiments have demonstrated that barbatic acid has some antioxidant and

antimicrobial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...

activity. It has cytotoxic and

genotoxic Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic s ...

activity against some tumour

cell lines An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...

. And ''

'' and ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' experiments using various cancer cell lines suggest that barbatic acid has antineoplastic and

pro-apoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

activities combined with a low toxicity.

References

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