Barbatic acid is an organic compound that is made by some

lichen A lichen ( , ) is a composite organism that arises from algae or cyanobacteria living among filaments of multiple fungi species in a mutualistic relationship.depsides. It is particularly common in the genera '' Usnea'' (the beard lichens) and '' Cladonia''.

History

The compound was first isolated in 1880 from the lichen ''

Usnea barbata ''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 ...

'' 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 bor ...

and Charles Groves. The compound coccellic acid, isolated from ''

Cladonia coccifera ''Cladonia coccifera'' or madame's cup lichen is a species of fruticose, cup lichen in the family Cladoniaceae. It was first described by Swedish lichenologist Carl Linnaeus in his 1753 work ''Species Plantarum''. German botanist Carl Ludwig Wi ...

'', 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. The repeated action of this enzyme produces an 8-carbon polyketide intermediate that is cyclized. Barbatic acid's IUPAC name is 2-hydroxy-4-(2-hydroxy-4-methoxy-3,6-dimethylbenzoyl)oxy-3,6-dimethylbenzoic acid. Its chemical formula is C₁₉H₂₀O₇; it has a molecular mass of 360.36

grams per mole In chemistry, the molar mass of a chemical compound is defined as the mass of a sample of that compound divided by the amount of substance which is the number of moles in that sample, measured in moles. The molar mass is a bulk, not molecular, p ...

. In its purified crystalline form, it exists as various forms: small

rhombic Rhombic may refer to: * Rhombus, a quadrilateral whose four sides all have the same length (often called a diamond) *Rhombic antenna, a broadband directional antenna most commonly used on shortwave frequencies * polyhedra formed from rhombuses, suc ...

prisms, long needles, or delicate thin sheets ( lamellae). Its melting point is . The crystal structure of the methyl ester 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, in the space group called P. In this crystal form, two highly substituted phenyl rings are bridged by an

ester group 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 ...

and are inclined towards each other at 106.1°. There are two strong intramolecular

hydrogen bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...

s between the hydroxyl substituents an the adjacent ester carbonyl groups. The crystal structure of pure barbatic acid, determined using single crystal

X-ray diffraction X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

analysis, was reported in 2019.

Synthesis

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors ** Organic synthesis, the chemical synthesis of organ ...

for barbatic acid was reported in 1975 using trifluoroacetic acid as a condensing agent. In 2022, a total synthesis 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 (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, 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'' molluscicidal activity of barbatic acid against the human parasite ''

Schistosoma mansoni A paired couple of ''Schistosoma mansoni''. ''Schistosoma mansoni'' is a water-borne parasite of humans, and belongs to the group of blood flukes (''Schistosoma''). The adult lives in the blood vessels ( mesenteric veins) near the human inte ...

'', it may have potential use in the large-scale control and/or eradication of

schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody s ...

. Other research has shown that it is non-toxic to human peripheral blood mononuclear cells at concentrations that are effective against the parasite. Barbatic acid inhibits photosynthesis by irreversible binding to the proteins in the

photosystem II Photosystem II (or water-plastoquinone oxidoreductase) is the first protein complex in the light-dependent reactions of oxygenic photosynthesis. It is located in the thylakoid membrane of plants, algae, and cyanobacteria. Within the photosystem ...

complex. Immobilised cells of the lichen ''

Cladonia miniata ''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 N ...

'' var. ''parvipes'' have been used to synthesise barbatic acid. The cells were given sodium acetate or calcium acetate as a precursor for phenol biosynthesis. Laboratory experiments have demonstrated that barbatic acid has some

antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...

and antimicrobial activity. It has

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

and genotoxic activity against some tumour cell lines. And '' in vitro'' and '' in vivo'' experiments using various cancer cell lines suggest that barbatic acid has antineoplastic and pro-apoptotic activities combined with a low toxicity.

References

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