Asnovolins A-G, Spiromeroterpenoids Isolated from the Fungus Aspergillus novofumigatus, and Suppression of Fibronectin Expression by Asnovolin E.

Seven novel spiromeroterpenoids, asnovolins A-G (1-7), one of which was shown to suppress fibronectin expression, were isolated from Aspergillus novofumigatus CBS117520 along with a known compound, novofumigatonin (8). The structures of asnovolins A-G were elucidated using MS and 2D-NMR data. Asnovolin E (5) suppressed fibronectin expression by normal human neonatal dermal fibroblast cells.

Isolation and structure elucidation of new phthalide and phthalane derivatives, isolated as antimicrobial agents from Emericella sp. IFM57991.

Three new phthalide derivatives, emefuranones A1, A2 and B (1-3); six new phthalane derivatives, emefuran A, B1, B2, C1, C2 and D (4-9); three new farnesylated phthalide derivatives, farnesylemefuranones A-C (10-12); xylarinol C (13); and emericelloxide (14), along with four known compounds (dustanin, sorbicillin, aspergillodiol and xylarinol A), were isolated from the culture extracts of Emericella sp. IFM57991. Structures of 1-14 were elucidated on the basis of spectroscopic analysis and chemical evidence. Compounds 4-7 and 13 showed moderate antibacterial activities against Bacillus subtilis.

Total synthesis of schizocommunin and revision of its structure.

A proposed structure for schizocommunin (Z)-1(hydroxy) and its geometric isomer (E)-1(hydroxy), which exist in a keto form, has been synthesized. However, the spectroscopic data of (Z)-1(keto) and (E)-1(keto) were not consistent with those reported for natural schizocommunin. After reinvestigating the spectral data for natural schizocommunin, we synthesized the quinazolinone derivative (Z)-2 as a revised structure for schizocommunin. All of the spectral data of (Z)-2 were completely identical to those reported for natural schizocommunin. (Z)-2 showed moderate antiproliferative activity.

Quinazolinobenzodiazepine Derivatives, Novobenzomalvins A-C: Fibronectin Expression Regulators from Aspergillus novofumigatus.

Three new quinazolinobenzodiazepine derivatives, novobenzomalvins A (1), B (2), and C (3), have been isolated as fibronectin expression regulators from Aspergillus novofumigatus CBS117520. The structures of 1 to 3 were established by spectroscopic and physicochemical analysis, and chemical investigation including the total synthesis of 1. Treatment with novo-benzomalvins A (1), B (2), C (3), and N-methylnovobenzomalvin A (5) increased the expression of fibronectin in normal human neonatal dermal fibroblast cells.

Novoamauromine and ent-Cycloechinulin: two new diketopiperazine derivatives from Aspergillus novofumigatus.

Two new diketopiperazine metabolites, novoamauromine (1) and ent-cycloechinulin (2) have been isolated from Aspergillus novofumigatus CBS117520. The structures of 1 and 2 were established on the basis of spectroscopic and chemical investigation, including a detailed comparison of the spectroscopic and physico-chemical data of amauromine (3) and cycloechinulin (4).

A new indoloditerpene derivative, penijanthine A, isolated from Penicillium janthinellum.

In a screen searching for new bioactive agents, a new indoloditerpene, penijanthine A (1), was isolated from Penicillium janthinellum IFM 55557. The structure of 1 was established on the basis of spectroscopic and chemical investigation, as well as detailed comparison with the spectroscopic and physico-chemical data of paxilline (2), which was isolated along with 1.

Antifungal cyclic depsipeptide, eujavanicin A, isolated from Eupenicillium javanicum.

In the course of searching for new antifungal agents, a new cyclic depsipeptide, eujavanicin A (1), was isolated from Eupenicillium javanicum as an antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established by spectroscopic and chemical investigations. The absolute stereochemistry was elucidated by Marfey's method and by chiral HPLC analysis.

Inhibitory effects of falconensins on 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema in mice.

Fifteen derivatives of falconensin were examined for their inhibitory activity against the induction of ear edema in mouse ear by application of 12-O-tetradecanoylphorbol-13-acetate (TPA). It was demonstrated that azaphilonoid falconensins exert inhibitory effects against TPA-induced inflammation in the ears of mice to a comparable degree as moascorubrin and indomethacin, which are known to have antitumor-promoting and anti-inflammatory effects. All compounds tested, except monomethylmitorubrin, inhibited the inflammatory activity induced by TPA.

Atopic cough-like cough hypersensitivity caused by active sensitization with protein fraction of Aspergillus restrictus strain A-17.

We examined the sensitivity of the cough reflex to inhaled citric acid in guinea pigs that had been actively sensitized with the protein fraction of Aspergillus restrictus strain A-17. The number of coughs elicited by an aerosol of 5% citric acid was significantly increased in the sensitized group compared to the non-sensitized group. The number of citric-acid-induced coughs in sensitized guinea pigs was dose-dependently and significantly reduced to the level in non-sensitized guinea pigs when animals were pretreated with fexofenadine, a selective histamine H1 receptor antagonist, 60min before citric acid inhalation. The bronchial responsiveness to inhaled methacholine or histamine in the sensitized group was not significantly heightened compared to the non-sensitized group. These results suggest that active sensitization with the protein fraction of A. restrictus by itself, that is without subsequent allergen challenge, enhances the excitability of cough receptors to tussive stimuli, and the physiologic features of this animal model are consistent with those of atopic cough.

Eujavanicols A-C, decalin derivatives from Eupenicillium javanicum.

Three new decalin derivatives, eujavanicols A-C (1-3), were isolated from an extract of Eupenicillium javanicum IFM 54704. Their structures were determined by chemical and spectroscopic methods.

Lepidepyrone, a new gamma-pyrone derivative, from Neolentinus lepideus, inhibits hyaluronidase.

In the course of screening for hyaluronidase (HAase) inhibitory agents, a new gamma-pyrone derivative, lepidepyrone, C(8)H(10)O(5), was isolated from the cultured mycelium of the mushroom Neolentinus lepideus TMC-1102 as a major HAase inhibitory compound (IC(50) 3.3 mM). The structure of lepidepyrone was established on the basis of spectroscopic investigation.

[Allergen activity of xerophilic fungus, Aspergillus restrictus].

BACKGROUND AND PURPOSE: The typical xerophilic fungi, Aspergillus restrictus, have been very frequently detected in house dust by low water activity medium. Since the composition of fungal allergens are affected culture and extract condition, we considered the influence in A. restrictus in order to develop new allergen of xerophilic fungi. METHOD: The 4 different extract of A. restrictus were obtained from various fermentation and extraction methods. These extracts were studied for specific IgE in sera of patients with asthma. The cross-reactivity between A. restrictus and A. fumigatus were analyzed by enzyme-linked immunosorbent assay (ELISA) inhibition. Then, component analysis of A. restrictus allergens was examined by SDS-PAGE and Western Blotting. RESULT: In ELISA, IgE antibodies against four extracts of A. restrictus were found in sera of 20-48%. In ELISA inhibition using sera obtained from 11 asthma patients, A. fumigatus antigen solution inhibited the reaction of A. restrictus with 5 asthma patients. CONCLUSION: These results indicated that A. restrictus may be important as a causative agent in adult asthma patients. However, it was suggested that some preparation methods of an extract influence activity. Furthermore, cross-reactivity was found between A. restrictus and A. fumigatus.

Two new dioxopiperazine derivatives, arestrictins A and B, isolated from Aspergillus restrictus and Aspergillus penicilloides.

In the course of searching for bioactive substances, two new dioxopiperazine derivatives, arestrictins A (1) and B (2), were isolated along with the known dioxopiperazine, cristatin A (3), and the known peptide, asperglucide (4), from the organic extract of the xerophilic fungi, Aspergillus restrictus and Aspergillus penicilloides. The absolute structures of 1 and 2, except for the configuration of the secondary alcohol in 1, were established by spectroscopic and chemical investigation. The absolute configuration of cristatin A (3) was also determined.

A new antifungal macrolide, eushearilide, isolated from Eupenicillium shearii.

In screening for antifungal substances, a new macrolide, eushearilide (1), was isolated from Eupenicillium shearii IFM54447. The structure of 1 was established to be 24-membered macrolide having a non-conjugated diene and a choline phosphate ester moetiy on the basis of detailed investigation of NMR, UV, IR and MS spectral data. Compound 1 showed antifungal activity against various fungi and yeasts, including human pathogens Aspergillus fumigatus, Trichophyton spp. and Candida spp.

Stereochemical course in water addition during LUP1-catalyzed triterpene cyclization.

Arabidopsis thaliana LUP1 (At1g78970) catalyzes the cyclization of oxidosqualene into lupeol and 3beta,20-dihydroxylupane (lupanediol). The stereochemical course of water addition to the lupanyl cation was studied. The X-ray crystal structure of lupanylepoxide 3,5-dinitrobenzoate established the configuration of epoxide as 20S. LiAlD4 reduction of the epoxide enabled the chemical shift assignment of prochiral methyl groups at C20 of lupanediol. Correlation of these methyl groups with biosynthetic lupanediol from [1,2-(13)C(2)] acetate established the stereochemical course of water addition. [reaction: see text].

Three new types of indoloditerpenes, emindole PA-PC, from Emericella purpurea. Revision of the structure of emindole PA.

Three new type indoloditerpenes, emindoles PA (1), PB (2), and PC (3), were isolated from the mycelium of Emericella purpurea along with the sesterterpenes variecolol and variecolactone, and the dicyanide derivatives epurpurins A to C. The structures of 1-3 were confirmed by the spectroscopic investigation. The structure of emindoles PA (1) was revised from our preliminary report. Emindoles PA (1), PB (2), and PC (3) are the indoloditerpenes having a new type of carbon skeleton.

New penicillide derivatives isolated from Penicillium simplicissimum.

Two new penicillide derivatives, secopenicillides A (3) and B (4), were isolated along with penicillide (1) and purpactin A (2), and altenusin (5) and dehydroaltenusin (6), the antifungal substances of this fungus, from the extract of Penicillium simplicissimum IFM 53375. The absolute structures of 3 and 4 were determined by spectroscopic investigation and chemical correlation to penicillide (1). The absolute configuration of purpactin A (2) was determined by the chemical method.