1-(3-フリル)-4-ヒドロキシペンタン-1-オン

0.84

0.84

Chloroform > 100 (mg/mL)

Methanol > 100 (mg/mL)

Water ~ 20 (mg/mL)

10% propylene glycol, 10% EtOH in water ~ 20 (mg/mL)

0.1 N HCl ~ 55 (mg/mL)

0.1 N NaOH < 3 (mg/mL)

SPECIFIC OPTICAL ROTATION: +7.86 DEG @ 25 °C/D (CARBON TETRACHLORIDE, 1.17%); MAXIMUM ABSORPTION (METHYL ALCOHOL): 211 NM (E= 6,100) SHOULDER; 251 NM (E= 2,970)

(c = 1.1,CCl4) [a]20D = 1.0 ± 0.2°

A REVIEW WITH 33 REFERENCES ON THE METABOLIC ACTIVATION OF TOXINS IN EXTRAHEPATIC TARGET ORGANS & TARGENT CELLS, WITH REFERENCES TO PULMONARY & RENAL TOXICITIES OF 4-IPOMEANOL.[BOYD MR ET AL; METABOLIC ACTIVATION OF TOXINS IN EXTRAHEPATIC TARGET ORGANS AND TARGET CELLS; DEV TOXICOL ENVIRON SCI 6(SCI BASIS TOXIC ASSESS) 141 (1980)]

A REVIEW OF THE EFFECT OF HEPATIC METABOLISM ON THE PRODUCTION & TOXICITY OF REACTIVE METABOLITES, INCLUDING IPOMEANOL, IN EXTRAHEPATIC ORGANS.[BOYD MR, STATHAM CN; THE EFFECT OF HEPATIC METABOLISM ON THE PRODUCTION AND TOXICITY OF REACTIVE METABOLITES IN EXTRAHEPATIC ORGANS; DRUG METAB REV 14(1) 35 (1983)]

IN RATS, BINDING OF BENZO(A)PYRENE METABOLITES WAS DECREASED 3-FOLD IN THE KIDNEY & 2-FOLD IN THE LIVER AFTER TREATMENT WITH 4-IPOMEANOL. NO EFFECT WAS DETECTED ON BENZO(A)PYRENE BINDING IN THE LUNG, BRAIN, OR SKELETAL MUSCLE.

TOXIC DOSES OF 4-IPOMEANOL PREFERENTIALLY DEPLETED RAT LUNG GLUTATHIONE. PRETREATMENT OF RATS WITH PIPERONYL BUTOXIDE, AN INHIBITOR OF THE METABOLIC ACTIVATION OF 4-IPOMEANOL, PREVENTED BOTH THE DEPLETION OF LUNG GLUTATHIONE & THE PULMONARY TOXICITY OF 4-IPOMEANOL.

DIETHYLMALEATE (DEM), AN AGENT WHICH DEPLETES TISSUE GLUTATHIONE (GSH), INCREASED THE COVALENT BINDING & TOXICITY OF 4-IPOMEANOL IN RATS. DEM TREATMENT PRODUCED NO SIGNIFICANT EFFECTS ON THE TISSUE DISTRIBUTION OF UNMETABOLIZED 4-IPOMEANOL. THE PULMONARY LEVELS OF BOTH THE COVALENTLY BOUND 4-IPOMEANOL EQUIVALENTS & THE 4-IPOMEANOL METABOLITES WERE INCREASED MARKEDLY BY DEM TREATMENT AT ALL TIME PERIODS EXAMINED. THESE DATA ARE CONSISTENT WITH THE VIEW THAT THE INCREASED PULMONARY COVALENT BINDING & TOXICITY OF 4-IPOMEANOL PRODUCED BY DIETHYLMALEATE PRETREATMENT IN RATS ARE DUE TO THE DEPLETION OF PULMONARY GSH BY THE DEM & NOT A MAJOR DEM-INDUCED ALTERATION IN THE TISSUE DISTRIBUTION OF THE PARENT 4-IPOMEANOL.

IN RATS, PHENOBARBITAL TREATMENT INCREASED THE URINARY EXCRETION OF NONBOUND 4-IPOMEANOL METABOLITES (IPOMEANOL-4-GLUCURONIDE), WHILE 3-METHYLCHOLANTHRENE TREATMENT DID NOT ALTER THEIR EXCRETION. THESE DATA INDICATE THAT THE DECREASED PULMONARY COVALENT BINDING & LETHALITY OF 4-IPOMEANOL IN THE RAT AFTER 3-METHYLCHOLANTHRENE & PHENOBARBITAL, WERE CAUSED BY ALTERATIONS IN THE TISSUE DISTRIBUTION OF THE PARENT COMPOUND.

THE FORMATION OF HIGHLY REACTIVE METABOLITES FROM 4-IPOMEANOL, A SELECTIVE LUNG TOXIN IN RODENTS & OTHER MAMMALS & A POTENT HEPATOTOXIN IN BIRDS, WAS STUDIED IN TISSUES FROM ROOSTERS & JAPANESE QUAIL IN VIVO. CONSISTENT WITH PREVIOUS IN VIVO STUDIES ON THE TARGET ORGAN SELECTIVITY FOR COVALENT BINDING & TOXICITY OF 4-IPOMEANOL METABOLITES IN BIRDS, THE RATES OF REACTIVE METABOLITE FORMATION WERE VERY HIGH IN BIRD LIVER MICROSOMES COMPARED TO AVIAN PULMONARY OR RENAL MICROSOMES WHERE THIS ACTIVITY WAS RELATIVELY VERY LOW OR ABSENT.

URINARY EXCRETION & METABOLISM OF 4-IPOMEANOL WAS STUDIED IN RATS INJECTED IP WITH THE RADIOLABELED COMPD. THERE WAS RAPID ELIMINATION OF RADIOACTIVITY IN THE URINE, AMOUNTING TO 47% OF THE ADMINISTERED DOSE WITHIN 4 HR. ONE MAJOR METABOLITE, IPOMEANOL 4-GLUCURONIDE, WAS IDENTIFIED. THE LARGE AMOUNT OF THIS METABOLITE EXCRETED SUGGESTS THAT 4-GLUCURONIDATION IS AN IMPORTANT DETOXICATION REACTION IN VIVO FOR 4-IPOMEANOL IN RATS.