Lichexanthone is an
organic compound in the structural class of chemicals known as
xanthones. Lichexanthone was first isolated and identified by Japanese chemists from a species of
leafy lichen in the 1940s. The compound is known to occur in many
lichens, and it is important in the
taxonomy of species in several
genera, such as Pertusaria and Pyxine. More than a dozen lichen species have a variation of the word lichexanthone incorporated as part of their
binomial name. The presence of lichexanthone in lichens causes them to
fluoresce a greenish-yellow colour under long-wavelength
UV light; this feature is used to help identify some species. Lichexanthone is also found in several plants (many are from the families
Annonaceae and
Rutaceae), and some species of
fungi that do not form lichens.
In lichens, the
biosynthesis of lichexanthone occurs through a set of
enzymatic reactions that start with the molecule
acetyl-CoA and sequentially add successive units, forming a longer chain that is
cyclized into a double-ring structure. Although it has been suggested that lichexanthone functions in nature as a
photoprotectant—protecting resident
algal populations (
photobionts) in lichens from high-intensity
solar radiation—its complete ecological function is not fully understood. Some
biological activities of lichexanthone that have been demonstrated in the laboratory include
antibacterial,
larvicidal, and
sperm motility-enhancing activities. Many lichexanthone
derivatives are known, some produced naturally in lichens, and others created
synthetically; like lichexanthone, some of these derivatives are also biologically active.
History
Lichexanthone was first reported by Japanese chemists
Yasuhiko Asahina and Hisasi Nogami in 1942. They isolated the
lichen product from Parmelia formosana[2] (known today as Hypotrachyna osseoalba), a lichen that is widespread in Asia.[3] Another early publication described its isolation from Parmelia quercina (now Parmelina quercina[4]).[5] Lichexanthone was the first
xanthone to be reported from lichens,[6] and it was given its name by Asahina and Nogami for this reason.[2]
Asahina and Nogami used a chemical method called potash fusion (
decomposition with a hot solution of the strong base
potassium hydroxide) on lichexanthone to produce
orcinol.[2] The earliest
syntheses of lichexanthone used
orsellinic aldehyde and
phloroglucinol as starting reactants in the
Tanase method.[7] This method, one of six standard ways of synthesising xanthone derivatives, enables the creation of partially
methylated polyhydroxyxanthones.[8] In the reaction, the two substrates, in the presence of
hydrochloric acid and
acetic acid, produce a
fluorone derivative that is subsequently
reduced to give a
xanthene derivative, which, after subsequent methylation and
oxidation, leads to a xanthone with three methoxy groups. Afterwards, one of the methoxy groups is
demethylated to yield lichexanthone.[2] A simpler synthesis, starting from
everninic acid (2-hydroxy-4-methoxy-6-methylbenzoic acid) and phloroglucinol,[7] was proposed in 1956.[9] These early syntheses also helped to confirm the structure of lichexanthone before
spectral methods of analysis were widely available.[6] In 1977, Harris and Hay proposed a biogenetically modelled synthesis of lichexanthone starting from the
polycarbonyl compound 3,5,7,9,11,13-hexaoxotetradecanoic acid. In this synthesis, an
aldolcyclization between positions 8 and 13 followed by a
Claisen cyclization between positions 1 and 6 leads to the formation of a group of compounds that includes lichexanthone.[10]
A standardized
high-performance liquid chromatography (HPLC) assay has been described to identify many lichen-derived substances, including lichexanthone and many other xanthones; because many xanthone
isomers have different
retention times, this technique can be used to identify complex mixtures of structurally similar derivatives.[26] The technique was later refined to couple the HPLC output with a
photodiode array detector to screen for xanthones based on their specific
ultraviolet–visible spectra. In this way, lichexanthone is detected by monitoring its retention time, and verifying the presence of three peaks representing wavelengths of maximum absorption (λmax) at 208, 242, and 310
nm.[27]
Occurrence
Although first isolated from foliose (leafy) Parmelia species, lichexanthone has since been found in a wide variety of lichens. For example, in the foliose genus Hypotrachyna, it is found in about a dozen species; when present, it usually completely replaces other cortical substances common in that genus, like
atranorin and
usnic acid.[12] The presence or absence of lichexanthone is a
character used in classifying species of the predominantly tropical genus Pyxine; of about 70 species in the genus, 20 contain lichexanthone. This represents the largest group of foliose lichens with the compound, as it is generally restricted to some groups of tropical
crustose lichens, chiefly pyrenocarps and
Graphidaceae.[28] The large genus Pertusaria relies heavily on thallus chemistry to distinguish and classify species, some of which differ only in the presence or absence of a single secondary chemical. Lichexanthone, norlichexanthone, and their chlorinated derivatives are common in this genus.[29]
Although normally considered a secondary metabolite of lichens, lichexanthone has also been isolated from several plants, listed here organized by
family:
Lichexanthone has also been reported to occur in the bark of Faramea cyanea, although in that case it was suspected to have originated from a lichen growing on the bark.[46] Additionally, two non-lichenised fungus species, Penicillium persicinum[47] and Penicillium vulpinum,[48] can synthesize lichexanthone.
Xanthones are known to have strong UV-absorbing properties.[20] In experiments using laboratory-grown
mycobionts from the lichen Haematomma fluorescens, the synthesis of lichexanthone was induced when young
mycelia were exposed to long-wavelength UV light (365 nm) for three to four hours every week over a time span of three to four months. In the natural lichen, the compound is present in both the outer
cortical layer of the
thallus and in the exciple (rim) of the
ascomata. Lichexanthone may function as a light filter to protect the UV-sensitive algal layer in lichens from high-intensity
solar radiation.[49] The presence of the
photoprotective chemical in the cortex may allow them to survive in otherwise inhospitable habitats, like on exposed trees in tropical areas or high mountains.[50] It has been pointed out, however, that lichexanthone is also found in lichens living in less stressed environments, and from species that are in families where cortical substances are rare. In some instances, similar or related species exist that lack cortical substances entirely, suggesting that the actual ecological function of lichexanthone is not fully understood.[51]
Related compounds
Norlichexanthone (1,3,6-trihydroxy-8-methylxanthone) differs from lichexanthone in having hydroxy rather than methoxy groups at positions 3 and 6.[11] In griseoxanthone C (1,6-dihydroxy-3-methoxy-8-methylxanthen-9-one), the methoxy at position 6 of lichexanthone is replaced with a hydroxy.[20] Dozens of
chlorinated lichexanthone
derivatives have been reported, some isolated from a variety of lichen species, and some produced synthetically. These derivatives are variously mono-, bi-, or trichlorinated with the chlorines at positions 2, 4, 5, and 7.[6] As of 2016, 62 molecules with the lichexanthone scaffold had been described, and another eight additional lichexanthone derivatives were considered "putative"–thought to exist in nature, but not yet discovered in lichens.[20]
The effects of chlorine
substituents on some structural and electronic properties of lichexanthones have been studied with
quantum mechanical theory, to better understand things such as
intramolecular interactions,
aromaticity of the three rings, interactions between
ionic and
halogen bonds, and
binding energies of
complexes formed between lichexanthone,
magnesium ion (Mg+2) and
NH3.[52] A series of lichexanthone derivatives were synthesized and assessed for antimycobacterial activity against Mycobacterium tuberculosis. These derivatives consisted of ω-
bromo and ω-aminoalkoxylxanthones; lichexanthone and several derivatives were found to have weak antimycobacterial activity. According to the authors, this
chemometrics approach was useful to correlate structural and chemical features with in vitro antimycobacterial activity among the group of ω-aminoalkoxylxanthones.[19]
Eponyms
Some authors have explicitly named lichexanthone in the
specific epithets of their published lichen species, thereby acknowledging the presence of this compound as an important
taxonomic characteristic. These
eponyms are listed here, followed by their
author citation and year of publication. All of these species occur in Brazil:
^Aghoramurthy, K.; Seshadri, T.R. (1953). "An improved synthesis of lichexanthone". Journal of Scientific and Industrial Research (India). 12B: 350–352.
^
abcdeMasters, Kye-Simeon; Bräse, Stefan (2012). "Xanthones from fungi, lichens, and bacteria: the natural products and their synthesis". Chemical Reviews. 112 (7): 3717–3776.
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abcRoberts, John C. (1961). "Naturally occurring xanthones". Chemical Reviews. 61 (6): 591–605.
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^Grover, P.K.; Shah, G.D.; Shah, R.C. (1956). "Xanthones: part V. A new synthesis of lichexanthone". Journal of Scientific and Industrial Research (India). 15B: 629–630.
^Harris, Thomas M.; Hay, James V. (1977). "Biogenetically modeled syntheses of heptaacetate metabolites. Alternariol and lichexanthone". Journal of the American Chemical Society. 99 (5): 1631–1637.
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^
abcHuneck, Siegfried (1996). Identification of Lichen Substances. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 209–212.
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abHale, Mason E. (1975). "A Revision of the Lichen Genus Hypotrachyna (Parmeliaceae) in Tropical America". Smithsonian Contributions to Botany (25). Washington: Smithsonian Institution Press: 10.
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^Letcher, R.M. (1968). "Chemistry of lichen constituents—VI: Mass spectra of usnic acid, lichexanthone and their derivatives". Organic Mass Spectrometry. 1 (4): 551–561.
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^Carvalho, Adriana E.; Alcantara, Glaucia B.; Oliveira, Sebastião M.; Micheletti, Ana C.; Honda, Neli K.; Maia, Gilberto (2009). "Electroreduction of lichexanthone". Electrochimica Acta. 54 (8): 2290–2297.
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^Feige, G.B.; Lumbsch, H.T.; Huneck, S.; Elix, J.A. (1993). "Identification of lichen substances by a standardized high-performance liquid chromatographic method". Journal of Chromatography A. 646 (2): 417–427.
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^Aptroot, André; Jungbluth, Patrícia; Cáceres, Marcela E.S. (2014). "A world key to the species of Pyxine with lichexanthone, with a new species from Brazil". The Lichenologist. 46 (5): 669–672.
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^Archer, Alan (1997). The Lichen Genus Pertusaria in Australia. Bibliotheca Lichenologica. Vol. 69. Berlin/Stuttgart: J. Cramer.
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^Suárez, Alírica I.; Blanco, Zuleyma; Compagnone, Reinaldo S.; Salazar-Bookaman, María M.; Zapata, Varlin; Alvarado, Claudia (2006). "Anti-inflammatory activity of Croton cuneatus aqueous extract". Journal of Ethnopharmacology. 105 (1–2): 99–101.
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^Okorie, Dominic A. (1976). "A new phthalide and xanthones from Anthocleista djalonensis and Anthocleista vogelli". Phytochemistry. 15 (11): 1799–1800.
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^Anyanwu, Gabriel O.; Onyeneke, Chukwu E.; Rauf, Khalid (2015). "Medicinal plants of the genus Anthocleista—A review of their ethnobotany, phytochemistry and pharmacology". Journal of Ethnopharmacology. 175: 648–667.
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^Tsamo, Armelle Tontsa; Melong, Raduis; Mkounga, Pierre; Nkengfack, Augustin Ephrem (2018). "Rubescins I and J, further limonoid derivatives from the stem bark of Trichilia rubescens (Meliaceae)". Natural Product Research. 33 (2): 196–203.
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^Calderón, Angela I.; Terreaux, Christian; Schenk, Kurt; Pattison, Phil; Burdette, Joanna E.; Pezzuto, John M.; Gupta, Mahabir P.; Hostettmann, K. (2002). "Isolation and structure elucidation of an isoflavone and a sesterterpenoic acid from Henriettella fascicularis". Journal of Natural Products. 65 (12): 1749–1753.
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^El-Seedi, Hesham R.; Hazell, Alan C.; Torssell, Kurt B.G. (1994). "Triterpenes, lichexanthone and an acetylenic acid from Minquartia guianensis". Phytochemistry. 35 (5): 1297–1299.
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^Sriyatep, Teerayut; Chakthong, Suda; Leejae, Sukanlaya; Voravuthikunchai, Supayang P. (2014). "Two lignans, one alkaloid, and flavanone from the twigs of Feroniella lucida". Tetrahedron. 70 (9): 1773–1779.
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^Jiménez, Carlos; Marcos, Manuel; Villaverde, Mary Carmen; Riguera, Ricardo; Castedo, Luis; Stermitz, Frank (1989). "A chromone from Zanthoxylum species". Phytochemistry. 28 (7): 1992–1993.
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^Ferrari, F.; Monache, G.Delle; de Lima, R.Alves (1985). "Two naphthopyran derivatives from Faramea cyanea". Phytochemistry. 24 (11): 2753–2755.
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^Wang, Long; Zhou, Han-Bai; C. Frisvad, Jens; A. Samson, Robert (2004). "Penicillium persicinum, a new griseofulvin, chrysogine and roquefortine C producing species from Qinghai province, China". Antonie van Leeuwenhoek. 86 (2): 173–179.
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^Lima, Edvaneide Leandro de; Mendonça, Cléverton de Oliveira; Aptroot, André; Cáceres, Marcela Eugenia da Silva (2013). "Two new species of Cryptothecia from NE Brazil". The Lichenologist. 45 (3): 361–365.
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^Aptroot, André; Souza, Maria Fernanda; Spielmann, Adriano Afonso (2021). "Two new crustose Cladonia species with strepsilin and other new lichens from the Serra de Maracaju, Mato Grosso do Sul, Brazil". Cryptogamie, Mycologie. 42 (8): 137–148.
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