rel-(4S,5R,10R)-10-[(R)-[(2R)-3,6-Dihydro-6-oxo-2H-pyran-2-yl]hydroxymethyl]-4,5,8,9,10,11-hexahydro-4,8-dihydroxy-5-[(1S)-1-hydroxyheptyl]-1H-cyclonona[1,2-c:5,6-c′]difuran-1,3,6-trione

520.52600

520.53

DTXSID20176998

NEEDLES FROM ETHYL ACETATE|Crystalline

176.89000

0.48920

1.45g/cm3

210-214 °C (decomp)

857.6ºC

288.5ºC

1.614

PARTIALLY SOL IN WATER, FAIRLY SOL IN ALC & ESTERS & VERY SOL IN ACETONE /RUBRATOXINS/|INSOL IN OILS OR CHLOROFORM /RUBRATOXINS/

2.9E-34mmHg at 25°C

THE ONLY DIFFERENCE BETWEEN THE RUBRATOXINS IS THAT ONE OF THE ANHYDRIDE GROUPS OF RUBRATOXIN B IS REDUCED TO THE LACTOL IN THE A TOXIN|Very soluble in acetone, moderately soluble in alcohol and esters and only sparingly soluble in water; completely insoluble in non-polar solvents /Rubratoxins/|Infra-red spectra reveal strong absorption in the carbonyl region...strong absorption at about 3500 cm-1 /Rubratoxins/|Unstable in alkaline solution

STABLE AT ROOM TEMP /RUBRATOXINS/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

THE FORMATION, CHEMICAL AND PHYSICAL PROPERTIES, ANALYSIS, AND BIOLOGICAL ACTIVITY OF RUBRATOXINS A AND B ARE REVIEWED WITH 43 REFERENCES.[NEWBERNE PM; PENICILLIUM RUBRUM- RUBRATOXINS; MYCOTOXINS: 163 (1974)]|A REVIEW WITH 12 REFERENCES. THE TOXICITY AND TERATOGENICITY OF RUBRATOXINS A AND B ARE DISCUSSED.[WILSON BJ, HARBISON RD; RUBRATOXINS; J AMER VET MED ASS 163(11) 1274 (1973)]

RUBRATOXINS MAY BE IMPORTANT IN POTENTIATING THE ACTIVITY OF COMPD SUCH AS AFLATOXINS SIMULTANEOUSLY PRODUCED IN AFFECTED FEEDS. /RUBRATOXINS/

RUBRATOXINS A & B ARE HEPATOTOXIC METABOLITES PRODUCED BY THE MOLDS PENICILLIUM RUBRUM & P PURPUROGENUM. THESE MOLDS OFTEN GROW IN FEEDSTUFFS ALONG WITH ASPERGILLUS SP; RUBRATOXINS & AFLATOXINS MAY COEXIST IN THE GRAIN OR FEED PRODUCT. THIS MEANS THAT AFLATOXICOSIS MAY BE COMPLICATED BY RUBRATOXINS & THAT THE CONDITIONS FAVORING AFLATOXIN PRODUCTION IN STORED FEEDS CAN ALSO FAVOR RUBRATOXIN.

AS WELL AS SERVING TO COMPLETE THE OXIDATION OF GLUCOSE TO CO2 & WATER, THE TRICARBOXYLIC ACID CYCLE ALSO PROVIDES INTERMEDIATES FOR THE BIOSYNTHESIS OF SOME SECONDARY METABOLITES, INCL THE RUBRATOXINS... THE FIRST STEP INVOLVES CONDENSATION OF DECANOIC ACID WITH OXALOACETIC ACID IN A MANNER ANALOGOUS TO THE FORMATION OF CITRIC ACID. SUBSEQUENT DEHYDRATION, DECARBOXYLATION & OXIDATION LEAD TO AN INTERMEDIATE ANHYDRIDE WHICH DIMERIZES TO FORM, AFTER FURTHER OXIDATION, RUBRATOXIN A. AT WHAT STAGE THE OXYGEN FUNCTIONS ARE INTRODUCED IS NOT CLEAR, &, IN PARTICULAR, SUCH A HYPOTHESIS WOULD MEAN THAT THE CARBOXYL GROUP OF THE ALPHA,BETA-UNSATURATED GAMMA-LACTONE WOULD BE DERIVED FROM THE METHYL CARBON OF ACETATE.|RUBRATOXIN A OCCURS AS THE MINOR METABOLITE ALONG WITH RUBRATOXIN B, THE MAJOR METABOLITE FROM.../PENICILLIUM RUBRUM & P PURPUROGENUM/.|A STERILE GLUCOSE-MINERAL SALTS BROTH WAS INOCULATED WITH SPORE SUSPENSIONS OR MYCELIAL PELLETS OF PENICILLIUM RUBRUM AND INCUBATED QUIESCENTLY FOR 14 DAYS. RUBRATOXINS WERE RECOVERED FROM CULTURE FILTRATES BY ETHER EXTRACTION AND RESOLVED BY TLC. TOXIN FORMATION WAS ENHANCED BY MALONATE BUT WAS NOT MARKEDLY AFFECTED BY ETHYL MALONATE, SHIKIMATE, AND ACETATE OR BY ISOCITRATE OR OXALOACETATE ADDED IN THE PRESENCE OF MALONATE. CITRATE, CIS-ACONITATE, ALPHA-KETOGLUTARATE, SUCCINATE, FUMARATE AND MALONATE WHEN PRESENT IN THE MEDIUM ALONE OR IN CONJUNCTION WITH MALONATE CAUSED A 15-50% REDUCTION IN RUBRATOXIN FORMATION. ACETYL-COA (10-15 MOL/FLAS) CAUSED AN 80% INCREASE IN TOXIN YIELD. AT 10-3 MOLAR, CITRATE STIMULATED RUBRATOXIN A PRODUCTION BY AS MUCH AS 100%. ABOVE 10-3 MOLAR, CITRATE INHIBITED TOXIN PRODUCTION. INCORPORATION OF (2-14)C-ACETATE INTO RUBRATOXIN WAS ENHANCED BY MALONATE AND FUMARATE + MALONATE. PYRUVATE + MALONATE PRODUCED A 40% INCREASE IN (2-14)C-ACETATE INCORPORATION INTO RUBRATOXIN. THE HIGHEST REDUCTION OF LABELED ACETATE INCORPORATION (36%) WAS CAUSED BY SUCCINATE OR ALPHA-KETOGLUTARATE COMBINED WITH MALONATE.|THE LIVER METABOLIZES RUBRATOXINS. THERE ARE A NUMBER OF METABOLITES. IN RATS, GLUCURONIDE & SULFATE CONJUGATES ARE EXCRETED IN BILE, APPARENTLY HYDROLYZED IN THE INTESTINE, & THE PARENT TOXIN MAY BE RESORBED IN AN ENTEROHEPATIC CYCLE. UNKNOWN METABOLITES ARE ALSO FORMED. /RUBRATOXINS/

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

MAXIMUM MOLD GROWTH AND TOXIN PRODUCTION WAS FAVORED BY 20% GLUCOSE. THE HIGHEST YIELD OF RUBRATOXIN A APPEARED IN 6 DAYS.

TLC DATA: ADSORBENT: SILICA GEL HF254; SOLVENT GLACIAL ACETIC ACID-METHANOL-CHLOROFORM, 2:20:80 VOL/VOL/VOL; DETECTION: A DARK SPOT AGAINST A GREEN FLUORESCENT BACKGROUND WHEN EXAMINED UNDER SHORTWAVE UV LIGHT; HAYES AW, WILSON BJ; APPL MICROBIOL 16: 1163 (1968).|A COLORIMETRIC METHOD FOR ASSAYING RUBRATOXIN A IN MIXT OF THE TWO TOXINS HAS BEEN REPORTED; MOSS MD, HILL IW; MYCOPATHOL MYCOLOGIA APPL 48: 81 (1970).|RUBRATOXINS A AND B WERE RESOLVED AS SHARP PEAKS IN THE ORDER A-B BY REVERSED-PHASE HIGH PRESSURE LIQUID CHROMATOGRAPHY ON A SMALL-PARTICLE (10 MUM) COLUMN IN 3 MINUTES BY AN ACETONITRILE-WATER-ETHYL ACETATE ELUTION SOLVENT (11:9.9:3), WITH DETECTION BY UV ABSORBANCE AT 254 NM.