Hideyuki Furukawa

Isolation and stereostructures of citreoviral, citreodiol, and epicitreodiol

Three new metabolites (citreoviral, citreodiol, and epicitreodiol) have been isolated from the mycelium of Penicillium citreo-viride B.(IFO 6050) and their stereostructures have been elucidated on the basis of their spectral data coupled with some chemical evidence. Furthermore, the absolute configurations of citreodiol and epicitreodiol have been determined by syntheses of the corresponding antipodes starting from L-rhamnose.

Structural and conformational studies on citreoviridinol and isocitreoviridinol: syntheses of some 2,6-dioxabicyclo[3.2.1]octanes

Abstract Isocitreoviridinol has been newly isolated from the mycelium of Penicillium citreo-viride B. (IFO 6050) together with citreoviridinol, and their stereostructures have also been elucidated by means of chemical method: the 2,6-dioxabicyclo[3.2.1]octanes have been made, one of which is regarded as a promising synthetic intermediate of citreoviridinol. In addition, isocitreoviridinol diacetate has been derived from citreoviridin in 3 steps.

Isolation and structure of citreopyrone, a metabolite of penicillium citreo-viride biourge

Abstract Citreopyrone isolated from the mycelium of Penicillium citreo-viride B. has been found to be 5-crotonoyl-4-methoxy-6-methyl-2-pyrone. This is the first naturally occurring pyrone with an acyl group at C5-position.

Isolation and stereostructures of neocitreoviridinol and epineocitreoviridinol

Both neocitreoviridinol and epineocitreoviridinol with a 2,5-dioxabicyclo[2.2.1]-heptane ring have been isolated as new metabolises of Penicillium citreo-viride B., and their stereostructures have also been elucidated on the basis of their spectral data coupled with molecular mechanics calculations. In addition, a promising synthetic intermediate for neocitreoviridinol has been made.

Suppressing effects of S-methyl methanethiosulfonate and diphenyl disulfide on mitomycin C-induced somatic mutation and recombination in Drosophila melanogaster and micronuclei in mice

S-Methyl methanethiosulfonate (MMTS) and diphenyl disulfide (DPDS) are temporary enzyme-sulfhydryl blocking agents. They are naturally occurring phytoalexin-like and synthetic substances known to be very potent bio-antimutagens in Escherichia coli B/r WP2. In the present paper, the suppressing effects of MMTS on mitomycin C (MMC)-induced mutant wing spots in the somatic mutation and recombination test (SMART) of Drosophila melanogaster, and of MMTS and DPDS on MMC-induced micronucleated peripheral reticulocytes are described. MMTS consistently reduced the numbers of MMC-induced small single, large single and twin spots per wing at a dose of 10-1000 micrograms/vial, in a dose-dependent manner. MMTS reduced the number of twin spots per wing on the spontaneous mutation at the dose of 1000 micrograms/vial. MMTS and DPDS dose-dependently reduced the frequencies of MMC-induced micronucleated peripheral reticulocytes at a dose of 10-40, and 3-100 micrograms/kg, respectively. Our results confirmed that enzyme-sulfhydryl blocking agents, such as MMTS and DPDS, are effective antimutagens in vivo too.

Biosynthesis of citreothiolactone, citreopyrone and pyrenocine B

13C NMR spectroscopy using INADEQUATE pulse sequence method has been used to deduce the labelling patterns of the three metabolites of Penicillium citreo-viride B. derived from [1,2-13C]acetate, indicating that their carbon skeletons consist of two different units [CH3COCH2COCH2COS-Enzyme and CH3COCH2COS-Enzyme].

Biosynthesis of Some Curvularin-Type Metabolites by a Hybrid Strain ME 0005 Derived from Penicillium citreo-viride B. IFO 6200 and 4629

13 C Nmr analyses were carried out to deduce the labeling patterns of the curvularin-type metabolites of the the hybrid strain ME 0005 derived from [1,2- 13 C 2 ] acetate, indicating that eight acetate molecules are incorporated into these metabolites. And citreofuran, 12-oxocurvularin, and 11β-hydroxy-12-oxocurvularin are presumably formed from curvularin by enzymatic oxygenation. In addition, the structure of 11β-hydroxy-12-oxocurvularin was also supported by the present experiments

Genotoxic activity in vivo of the naturally occurring glucoside, cycasin, in the Drosophila wing spot test.

Cycasin, methylazoxymethanol-beta-glucoside, is a naturally occurring carcinogenic compound. The genotoxicity of cycasin was assayed in the Drosophila wing spot test. Cycasin induced small single and large single spots on feeding at 10 mumol/g medium. The presence of these spots indicates that cycasin is genotoxic in Drosophila melanogaster. Microorganisms which showed beta-glucosidase activity for cleaving cycasin to toxic aglycon were isolated from gut flora of the Drosophila larvae. Consequently, the Drosophila wing spot test would be useful for mutagenicity screening of other naturally occurring glucosides.

Low-Level Chemiluminescence and Life Span of Drosophila melanogaster

Spontaneous photon emission (chemiluminescence, CL) as a monitor of free radical evolution in Drosophila melanogaster which had been maintained at 25 or 30 degrees C for 5 days after emergence was measured. When maintained at 30 degrees C the fly CL intensity was stronger than at 25 degrees C. Under the condition of the higher temperature, the fly life span was shorter (mean life span = 29 days at 30 degrees C and 63 days at 25 degrees C), and oxygen consumption (3.7 microliters/mg.h at 25 degrees C, 4.9 microliters/mg.h at 30 degrees C) and the mobility (movement distance = 25 mm/min at 25 degrees C, 700 mm/min at 30 degrees C) increased, together with augmentation of phospholipid hydroperoxide in the fly total lipids. The CL spontaneously emitted from fly homogenate was decreased by the free radical scavengers both in experiments in vivo and in vitro. The hypothesis is proposed that as the oxygen metabolism grows active, the chemiluminescent reactions that involve oxygen-dependent free radical metabolism, including membrane phospholipid hydroperoxidation, contribute to the acceleration of senescence of fly bodies.

Low-level chemiluminescence from Drosophila melanogaster fed with chemical mutagens polycyclic aromatic hydrocarbon quinones and a carcinogenic bracken fern

The spontaneous photon emission (chemiluminescence) from Drosophila melanogaster fed chemical mutagens, polycyclic aromatic hydrocarbon quinones, and a carcinogenic bracken fern was studied. The fly chemiluminescence was evidently enhanced by mutagen or carcinogen administration and was increased proportionally to the administered amount of tested compound. Strong chemiluminescence was observed especially at the larval stage. Living larvae emitted stronger chemiluminescence than their homogenate. The chemiluminescence from Drosophila melanogaster fed polycyclic aromatic hydrocarbon quinones showed a linear relation with the mutation frequency in the Drosophila wing spot test. The chemiluminescence from flies fed a bracken fern decreased by the addition of free radical scavengers and active oxygen quenchers. The phosphatidylcholine hydroperoxide concentration in the flies was increased proportionally with the chemiluminescence intensity. It seems that the free radical formation is stimulated as shown by the enhanced chemiluminescence in mutagen- or carcinogen-dosed flies, and as a result, lipid peroxide accumulation accompanies mutation in Drosophila melanogaster.