Roquefortine C

Roquefortine C is a mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines[1] produced by various fungi, particularly species from the genus Penicillium.[2] It was first isolated from a strain of Penicillium roqueforti, a species commercially used as a source of proteolytic and lipolytic enzymes during maturation of the blue-veined cheeses, Roquefort, Danish Blue, Stilton and Gorgonzola.

Roquefortine C
Chemical structure of roquefortine C
Names
Preferred IUPAC name
(3E,5aS,10bR,11aS)-3-[(1H-Imidazol-5-yl)methylidene]-10b-(2-methylbut-3-en-2-yl)-6,10b,11,11a-tetrahydro-2H-pyrazino[1′,2′:1,5]pyrrolo[2,3-b]indole-1,4(3H,5aH)-dione
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
UNII
  • InChI=1S/C22H23N5O2/c1-4-21(2,3)22-10-17-18(28)25-16(9-13-11-23-12-24-13)19(29)27(17)20(22)26-15-8-6-5-7-14(15)22/h4-9,11-12,17,20,26H,1,10H2,2-3H3,(H,23,24)(H,25,28)/b16-9+/t17-,20-,22+/m0/s1 ☒N
    Key: SPWSUFUPTSJWNG-JJUKSXGLSA-N ☒N
  • InChI=1/C22H23N5O2/c1-4-21(2,3)22-10-17-18(28)25-16(9-13-11-23-12-24-13)19(29)27(17)20(22)26-15-8-6-5-7-14(15)22/h4-9,11-12,17,20,26H,1,10H2,2-3H3,(H,23,24)(H,25,28)/b16-9+/t17-,20-,22+/m0/s1
    Key: SPWSUFUPTSJWNG-JJUKSXGLBA
  • CC(C)(C=C)[C@@]12C[C@H]3C(=O)N/C(=C/c4cnc[nH]4)/C(=O)N3[C@@H]1Nc5c2cccc5
Properties
C22H23N5O2
Molar mass 389.5 g/mol
Appearance White to off-white solid
Soluble in ethanol, methanol, DMF or DMSO
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Roquefortine C is a cyclodipeptide mycotoxin derived from the diketopiperazine cyclo(Trp-dehydro-His) and is a relatively common fungal metabolite produced by a number of Penicillium species. It is also considered one of the most important fungal contaminants of carbonated beverages, beer, wine, meats, cheese and bread.[3] At high doses roquefortine C is classified as a toxic compound.[4] Although it is a potent neurotoxin[5][6] at high doses, at low concentrations of 0.05 to 1.47 mg/kg that occur in domestic cheeses, it was found to be "safe for the consumer".[7] The mechanisms underlying its toxicity and metabolism have been investigated by studying its interaction with mammalian cytochrome P450 enzymes.[4] In addition to these toxic properties, roquefortine C reportedly possesses bacteriostatic activity against gram-positive bacteria,[8] but only in those organisms containing haemoproteins.[4][9]

Roquefortine C contains the unusual E-dehydrohistidine moiety, a system that typically undergoes facile isomerization under acidic, basic, or photochemical conditions to isoroquefortine C, the 3,12 double-bond Z-isomer of roquefortine C.[10]

Isomerisation of Roquefortine C to Isoroquefortine C
Isomerisation of Roquefortine C to Isoroquefortine C

However isoroquefortine C is not a natural product and in contrast to roquefortine C does not bind iron. Both have been synthesised.[10]

References
  1. Borthwick AD (2012). "2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products". Chemical Reviews. 112 (7): 3641–3716. doi:10.1021/cr200398y. PMID 22575049.
  2. Kokkonen M, Jestoi M, Rizzo A (2005). "The effect of substrate on mycotoxin production of selected Penicillium strains". International Journal of Food Microbiology. 99 (2): 207–14. doi:10.1016/j.ijfoodmicro.2004.08.014. PMID 15734568.
  3. Borthwick AD, Da Costa NC (2017). "2,5-Diketopiperazines in Food and Beverages: Taste and Bioactivity". Critical Reviews in Food Science and Nutrition. 57 (4): 718–742. doi:10.1080/10408398.2014.911142. PMID 25629623. S2CID 1334464.
  4. Aninat C, Hayashi Y, André F, Delaforge M (July 2001). "Molecular requirements for inhibition of cytochrome P450 activities by roquefortine". Chemical Research in Toxicology. 14 (9): 1259–1265. doi:10.1021/tx015512l. PMID 11559041.
  5. SCBT. "Roquefortine - A potent neurotoxin produced most notably by Penicillium species". {{cite journal}}: Cite journal requires |journal= (help)
  6. EPA. "Penicillium roqueforti Final Risk Assessment". {{cite journal}}: Cite journal requires |journal= (help)
  7. Finoli C, Vecchio A, Galli A, Dragoni I (February 2001). "Roquefortine C occurrence in blue cheese". J. Food Prot. 64 (2): 246–51. doi:10.4315/0362-028x-64.2.246. PMID 11271775.
  8. Kopp-Holtwiesche B, Rehm HJ (December 1989). "Antimicrobial action of roquefortine". Journal of Environmental Pathology, Toxicology and Oncology. 10 (1–2): 41–44. PMID 2231314.
  9. Aninat C, Andre F, Delaforge M (April 2005). "Oxidative metabolism by P450 and function coupling to efflux systems: modulation of mycotoxin toxicity". Food Additives and Contaminants. 22 (4): 361–368. doi:10.1080/02652030500073287. PMID 16019806. S2CID 9880652.
  10. Shangguan N, Hehre WJ, Ohlinger WS, Beavers MP, Joullie MM (April 2008). "The total synthesis of roquefortine C and a rationale for the thermodynamic stability of isoroquefortine C over roquefortine C". Journal of the American Chemical Society. 130 (19): 6281–6287. doi:10.1021/ja800067q. PMID 18412344.
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