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Erythrin is a lichen secondary metabolite in the depside class. It is the D-erythritol ester of lecanoric acid and occurs especially in lichens of the genus Roccella, although it has also been reported from other members of the order Arthoniales. Historically, erythrin-containing Roccella lichens formed part of the raw material used to make orchil and cudbear dyes.

History

Erythrin was isolated from dye lichens of the genus Roccella by the early 19th century.[1] In 1845, Edward Schunck re-examined Roccella tinctoria, reported that his results did not fully agree with earlier analyses, referred to the principal crystalline constituent as “erythric acid”, and showed that it yielded orcin on alkaline decomposition.[2] Later 19th-century work by Edward Schunck, John Stenhouse and Oswald Hesse connected it with lecanoric acid and erythritol, the latter being first obtained by hydrolysis of erythrin.[1] By 1914, however, erythrin’s constitution was still under debate. Ernst Zerner reviewed earlier structural proposals by de Luynes and Oswald Hesse, rejected them on the basis of erythrin’s acidic properties and its behaviour on hydrolysis and alcoholysis, and proposed a revised structure.[3] This chemistry gave the compound practical importance in the orchil and cudbear dye trade, because hydrolysis of erythrin ultimately leads to orcinol, a precursor of orcein pigments.[1]

Modern structural work began with studies of Roccella montagnei. In 1940, V. Subba Rao and Tiruvengadam Rajagopala Seshadri described erythrin as one of the principal chemical constituents of that lichen and proposed a close relationship to lecanoric acid.[4] Two years later, they published a constitutional study concluding that erythrin is the erythrityl ester of lecanoric acid.[5] The assignment was later supported by laboratory synthesis of racemic erythrin in 1966.[6]

Chemistry

Erythrin is an orcinol-type depside with the molecular formula C20H22O10.[7] Structurally, it can be regarded as lecanoric acid in which the remaining carboxyl group is esterified with erythritol.[5][7] Hydrolysis yields lecanoric acid and erythritol, while further hydrolysis of lecanoric acid produces orsellinic acid.[5] Early workers described erythrin as forming bundles of pale yellow needles with a melting point of 156–157 °C.[4][7] The natural product is optically active,[5] a standard reference work gives a specific rotation of [α]D +8.0 for erythrin crystallised from methanol.[7]

In a study of the water solubility of common lichen compounds, erythrin was the most soluble substance examined, dissolving to 57 mg/l at 25 °C. The authors attributed this relatively high solubility chiefly to the additional alcoholic hydroxy groups in its erythritol side chain, and suggested that such solubility could allow lichen compounds to act as metal-complexing agents in rock weathering.[8]

Synthetic work has mainly served to confirm the structure rather than to produce the compound on a practical scale. Racemic erythrin was synthesised in 1966 by building the erythritol side chain onto lecanoric acid through a cis-2-butene-1,4-diol intermediate, followed by hydroxylation and loss of the ethoxycarbonyl group. The final optically inactive product matched natural erythrin in its ultraviolet and infrared spectra, and the hexaacetate prepared from the synthetic product likewise matched the corresponding derivative obtained from natural erythrin.[6] A later biomimetic synthesis produced both enantiomers of erythrin in stereochemically defined form. Comparison of the synthetic products with an authentic natural sample, including chiral HPLC analysis and optical rotation data, supported assignment of the natural compound as (+)-erythrin with the (2R,3S) configuration.[9] A still shorter synthesis of (-)-erythrin was reported in 2013. In that route, two orsellinic-acid-derived intermediates were coupled, and the resulting benzodioxinone derivative was then reacted with benzyl-protected D-erythritol before final hydrogenolysis furnished (-)-erythrin. The authors presented this method as requiring fewer synthetic steps than earlier routes.[10]

Occurrence and chemotaxonomy

Roccella gracilis is one of several members of the genus Roccella that contain erythrin.

Roccella montagnei is the classic source of erythrin.[4] Subsequent taxonomic and chemical studies have reported it from numerous species of Roccella.[11][12] In a 2020 comparison of five coastal Roccella species, erythrin was detected in all five, and the authors also compiled earlier reports indicating its presence in about 18 of the roughly 54 taxa then recognised in the genus.[12]

The compound is not confined to Roccella. It has also been reported from other Arthonialean lichens, including species of Dirina and Opegrapha.[13][14][15] Broader chemotaxonomic surveys of the families Opegraphaceae and Arthoniaceae likewise recorded erythrin and lecanoric acid as characteristic constituents in parts of those groups.[16][17]

Because closely related lichens can differ in whether they produce erythrin, lecanoric acid, or both, the compound has been used since at least the late 1960s as a chemotaxonomic character.[13][14][15] Modern authors have described it as a chemotaxonomic marker for Roccella,[18] and earlier Indian workers used erythrin together with roccellic acid to detect Roccella material in mixed lichen collections.[19]

Identification

Classical identification of erythrin relied on solvent extraction, recrystallisation, melting point, and simple colour reactions.[4][19] In alcoholic solution it gives a violet reaction with ferric chloride and an orange-red reaction with calcium hypochlorite (bleaching powder).[4] In routine lichenology, thalli containing erythrin often give a red reaction in the C spot test, and standard reference works list its behaviour in thin-layer chromatography and high-performance liquid chromatography.[20][7]

Later work added spectroscopic and mass-spectrometric methods. Reference works record ultraviolet, infrared, nuclear magnetic resonance and mass spectra for erythrin,[7] and published MS/MS studies describe a characteristic fragmentation pattern for the compound.[21]

Biosynthesis

Like other lichen depsides, erythrin is thought to arise from fungal polyketide biosynthesis.[20] Its aromatic core corresponds to lecanoric acid, and heterologous expression experiments with a lichen non-reducing polyketide synthase have shown that a single enzyme can assemble the two phenolic rings and join them by an ester linkage to form the depside core.[22]

Biological activity

Compared with many other lichen products, erythrin itself has received little direct pharmacological study. A 2023 review of lichen depsides listed it among compounds that remained poorly investigated biologically.[23] Published laboratory work has focused more on synthetic erythrin derivatives than on erythrin itself.[24]

References

  1. ^ a b c Perkin, Arthur George; Everest, Arthur Ernest (1918). The Natural Organic Colouring Matters. London: Longmans, Green and Co.
  2. ^ Schunck, Edward (1845). “CLXVII. On the substances contained in the Roccella tinctoria“. Memoirs and Proceedings of the Chemical Society. 3: 144–154. doi:10.1039/mp8450300144.
  3. ^ Zerner, Ernst (1914). “Die Struktur des Erythrins” [The structure of erythrin]. Monatshefte für Chemie und verwandte Teile anderer Wissenschaften (in German). 35 (8): 1021–1024. doi:10.1007/bf01519595.
  4. ^ a b c d e Rao, V.S.; Seshadri, T.R. (1940). “Chemical investigation of Indian lichens. Part I. Chemical components of Roccella montagnei“. Proceedings of the Indian Academy of Sciences, Section A. 12: 466–471. doi:10.1007/BF03172443.
  5. ^ a b c d Rao, V.S.; Seshadri, T.R. (1942). “Chemical examination of Indian lichens. Part VI. Constitution of erythrin”. Proceedings of the Indian Academy of Sciences, Section A. 16: 23–28. doi:10.1007/BF03177732.
  6. ^ a b Manaktala, S.K.; Neelakantan, S.; Seshadri, T.R. (1966). “Synthesis of (±) montagnetol and (±) erythrin”. Tetrahedron. 22 (7): 2373–2376. doi:10.1016/S0040-4020(01)82157-8.
  7. ^ a b c d e f Huneck, Siegfried; Yoshimura, Isao (1996). Identification of Lichen Substances. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 254–255. ISBN 978-3-642-85245-9.
  8. ^ Iskandar, I.K.; Syers, J.K. (1971). “Solubility of lichen compounds in water: pedogenetic implications”. The Lichenologist. 5 (1–2): 45–50. Bibcode:1971ThLic…5…45I. doi:10.1017/s0024282971000082.
  9. ^ Basset, Jean-François; Leslie, Colin; Hamprecht, Dieter; White, Andrew J.P.; Barrett, Anthony G.M. (2010). “Studies on the resorcylates: biomimetic total syntheses of (+)-montagnetol and (+)-erythrin”. Tetrahedron Letters. 51 (5): 783–785. doi:10.1016/j.tetlet.2009.11.134.
  10. ^ Kumbaraci, Volkan; Gunduz, Hande; Karadeniz, Meric (2013). “Facile syntheses of (−)-montagnetol and (−)-erythrin”. Tetrahedron Letters. 54 (47): 6328–6330. doi:10.1016/j.tetlet.2013.09.071.
  11. ^ Tehler, Anders; Irestedt, Martin; Wedin, Mats; Ertz, Damien (2010). “The Old World Roccella species outside Europe and Macaronesia: taxonomy, evolution and phylogeny”. Systematics and Biodiversity. 8 (2): 223–246. Bibcode:2010SyBio…8..223T. doi:10.1080/14772001003789554.
  12. ^ a b Ferron, Solenn; Berry, Olivier; Olivier-Jimenez, Damien; Rouaud, Isabelle; Boustie, Joël; Lohézic-Le Dévéhat, Françoise; Poncet, Rémy (2020). “Chemical diversity of five coastal Roccella species from mainland France, the Scattered Islands, and São Tomé and Príncipe”. Plant and Fungal Systematics. 65 (2): 247–260. doi:10.35535/pfsyst-2020-0021.
  13. ^ a b Huneck, Siegfried; Follmann, Gerhard (1968). “Über das Vorkommen von Erythrin und Lecanorsäure in einigen Dirina-Arten. 51. Mitteilung: Über Flechteninhaltsstoffe” [On the occurrence of erythrin and lecanoric acid in some Dirina species. 51st communication: On lichen substances]. Die Pharmazie (in German). 23: 156–157.
  14. ^ a b Huneck, Siegfried; Follmann, Gerhard (1968). “Notes on lichen substances LVII: the occurrence of erythrin in Opegrapha platycarpa (nyl.) nyl”. The Bryologist. 71 (3): 266. doi:10.1639/0007-2745(1968)71[266:nolslt]2.0.co;2.
  15. ^ a b Follmann, Gerhard; Huneck, Siegfried (1969). “Notes on lichen substances LVI. On the occurrence of erythrin in Chiodecton cretaceum Zahlbr”. The Lichenologist. 4 (2): 194–195. Bibcode:1969ThLic…4..194F. doi:10.1017/S002428296900020X.
  16. ^ Follmann, Gerhard; Huneck, Siegfried (1969). “Mitteilungen über Flechteninhaltsstoffe. LXVI. Zur Phytochemie und Chemotaxonomie der Opegraphaceae” [Communications on lichen substances. LXVI. On the phytochemistry and chemotaxonomy of the Opegraphaceae]. Österreichische Botanische Zeitschrift (in German). 117 (1): 7–13. Bibcode:1969PSyEv.117….7F. doi:10.1007/BF01376934.
  17. ^ Huneck, Siegfried; Follmann, Gerhard (1969). “Mitteilungen über Flechteninhaltsstoffe. LXIX. Zur Phytochemie und Chemotaxonomie der Arthoniaceae” [Communications on lichen substances. LXIX. On the phytochemistry and chemotaxonomy of the Arthoniaceae]. Österreichische Botanische Zeitschrift (in German). 117 (2): 163–175. Bibcode:1969PSyEv.117..163H. doi:10.1007/BF01379521.
  18. ^ Duong, T.-H.; Beniddir, M.A.; Genta-Jouve, G.; Aree, T.; Ferron, S.; Boustie, J.; Chavasiri, W.; Roussi, F. (2017). “New erythritol derivatives from the fertile form of Roccella montagnei“. Phytochemistry. 137: 156–164. Bibcode:2017PChem.137..156D. doi:10.1016/j.phytochem.2017.02.012. PMID 28222890.
  19. ^ a b Seshadri, T.R.; Subramanian, S. Sankara (1949). “Chemical investigation of Indian lichens. Part VIII. Some lichens growing on sandal trees (Ramalina tayloriana and Roccella montagnei)”. Proceedings of the Indian Academy of Sciences, Section A. 30 (1): 15–22. doi:10.1007/BF03049170.
  20. ^ a b Elix, John A. (2014). A Catalogue of Standardized Chromatographic Data and Biosynthetic Relationships for Lichen Substances (PDF) (3rd ed.). Canberra: John A. Elix.
  21. ^ Musharraf, Syed G.; Kanwal, Shehnaz; Thadhani, V.M.; Choudhary, M.I. (2015). “Rapid identification of lichen compounds based on the structure–fragmentation relationship using ESI-MS/MS analysis”. Analytical Methods. 7 (15): 6066–6076. doi:10.1039/C5AY01091H.
  22. ^ Kealey, James T.; Craig, James P.; Barr, Philip J. (2021). “Identification of a lichen depside polyketide synthase gene by heterologous expression in Saccharomyces cerevisiae“. Metabolic Engineering Communications. 13 e00172. doi:10.1016/j.mec.2021.e00172. PMC 8365352. PMID 34430202.
  23. ^ Ureña-Vacas, I.; González-Burgos, E.; Gómez-Serranillos, M.P.; Divakar, P.K. (2023). “Lichen depsides and tridepsides: progress in pharmacological approaches”. Journal of Fungi. 9 (1) 116. doi:10.3390/jof9010116. PMC 9866793. PMID 36675938.
  24. ^ Thadhani, V.M.; Choudhary, M.I.; Khan, S.; Karunaratne, V. (2010). “Novel entry into 5-decarboxydibenzofurans via Smiles rearrangement of the lichen para-depside, erythrin”. Journal of Chemical Research. 34 (3): 154–157. doi:10.3184/030823410X12677394014276.