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During the search for new antitrypanosomal drug leads, four antitrypanosomal compounds, of three depsipeptides and one nortriterpenoid, were isolated from cultures of the mutant strain IU-3 of the insect pathogenic fungus Ophiocordyceps coccidiicola NBRC 100683. Their structures were identified by the analysis of high resolution-electron ionization (HR-EI)-MS and HR-FAB-MS, and (1)H- and (13)C-NMR spectra, including extensive two dimensional (2D)-heteronuclear NMR experiments, and comparison with literature data for destruxin A (1), destruxin B (2), destruxin E chlorohydrin (3) and helvolic acid (4). Compounds 1-4 showed in vitro antitrypanosomal activity against Trypanosoma brucei brucei GUTat3.1 with IC50 values of 0.33, 0.16, 0.061 and 5.08 µg/mL, respectively.

Sparassis crispa (SC), known as Hanabiratake in Japanese, is an edible mushroom with various medicinal properties. We isolated 3 novel phthalides, designated hanabiratakelide A (1), B (2), and C (3), from the SC fruit body. In this investigation, 3 known phthalides (4—6), ubiquinone-9, and 2 known unsaturated fatty acids were also isolated. Their structures were elucidated primarily through extensive NMR experiments. The isolated compounds 1—6 were tested for their anti-oxidant activity. The in vitro superoxide dismutase-like activity of the 3 hanabiratakelides was stronger than that of vitamin C. The compounds also exerted inhibitory effects on lipopolysaccharide-stimulated nitric oxide and prostaglandin E2 production by a murine macrophage cell line, RAW264. In addition, the growth of the colon cancer cell lines Caco-2 and colon-26 was significantly inhibited by treatment with the 3 hanabiratakelides. In vivo, the frequency of azoxymethane-induced aberrant crypt foci was reduced in SC-fed F344/N rats compared to rats fed a standard diet. In conclusion, 3 novel phthalides, hanabiratakelides, derived from SC were shown to possess anti-oxidant, anti-inflammatory, and anti-tumor activity.

Biotransformation of the aristolane-type sesquiterpene hydrocarbon (+)-1(10)-aristolene (1) from the crude drug Nardostachys chinensis and of the 2,3-secoaromadendrane-type sesquiterpene lactone plagiochilide (2) from the liverwort Plagiochila fruticosa by three microorganisms, Chlorella fusca var. vacuolata, Mucor species, and Aspergillus niger was investigated. C. fusca var. vacuolata and Mucor sp. introduced oxygen function into the cyclohexane ring of aristolene while A. niger oxidized stereoselectively one methyl of the 1,1-dimethyl group on the cyclopropane ring of aristolanes and 2,3-secoaromadendrane to give C-12 primary alcohol and C-12 carboxylic acid. The possible metabolic pathway of the formation of new metabolites is discussed. The stereostructures of new metabolites were established by a combination of NMR spectroscopy including HMBC and NOESY, X-ray crystallographic analysis, and chemical reaction.

The aim of this study was to discover a novel agent that suppresses nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells. We carried out a screening test in fifteen azaphilone compounds, which were isolated from xylariaceous inedible mushrooms. The structure-activity relationship was discussed; accordingly, azaphilones were divided into five groups based on the functional groups attached to the main azaphilone backbone. Rubiginosin A, an azaphilone with an orsellinic acid moiety attached to the bicyclic azaphilone through an ester linkage, showed potential inhibitory activity. To clarify the mechanism involved, total RNA extraction, followed by RT-PCR for inducible nitric oxide synthase (iNOS) and finally electrophoresis on agarose gel were performed. These findings indicated that suppression of the LPS-induced NO production of rubiginosin A is due to the inhibition of iNOS protein synthesis.

Reboulia hemisphaerica, the thalloid liverwort, contained four new cyclomyltaylane- and two new ent-beta-chamigrane-type sesquiterpenoids of which the absolute stereostructures were established by a combination of two-dimensional NMR spectroscopy, X-ray crystallographic analysis, and the modified Mosher's method. Cyclomyltaylan-5alpha-ol and ent-beta-chamigren-1alpha-ol were biotransformed by the fungus Aspergillus niger to afford new oxygenated matabolites. Their structures were also elucidated in the same manner as described above.

An unusual oxidative transformation of α, β-unsaturated γ-lactone of the cardenolide gitoxin (1a) by tetra-n-butylammonium fluoride (TBAF) is reported. The structure of the product (2a) was finally confirmed by an X-ray crystal structure analysis of its genin (2b). The oxidation proceeded also in the presence of CsF, and KF + 18-crown-6.

A sesquiterpene alcohol with a new rearranged pinguisane carbon skeleton, which is named a neo-pinguisane type, has been isolated from the ether extract of the liverwort Dicranolejeunea yoshinagana (Hatt.) Mizut., together with two new pinguisane-type sesquiterpenoids and previously known deoxopinguisone and ptychanolide. Their structures were established by spectroscopic means.

Eight new sacculatane-type diterpenoids, named 12-deoxy-1β, 11α-dihydroxy-sacculatanolide (1), 11α-hydroxysacculatanolide (2), pellianolactones A, B, (3, 4), 1β, 11α-dihydroxysacculatanolide (5), 1β-hydroxysacculatal (6), 1β-hydroxy-isosacculatal (7), and 1β-hydroxysacculatanolide (8), have been isolated from the liverwort Pellia endiviifolia.

Three novel polyacetylene triglycerides, named lycogarides A-C (1-3), have been isolated from the Myxomycetes Lycogala epidendrum. Their relative structures have been established by a combination of two-dimension NMR spectroscopy and chemical degradation. The absolute structures of compounds 1 and 2 were deduced from the modified Mosher's and dibenzoate exiton chirality methods of their derivatives.

Three novel azaphilone derivatives, daldinins A∼C, have been isolated from the fungus (Ascomycetes) Daldinia concentrica. Their structures including the absolute configuration have been established by a combination of high resolution NMR and CD spectra, X-ray crystallographic analysis, and chemical degradation.

The stereostructure of plagiochiline A (1) isolated from the liverwort Plagiochila fruticosa has been established by X-ray crystallographic analysis. Plagiochiline A was converted into plagiochilal B (2) and furanoplagiochilal (3) by human saliva, and stearoylvelutinal (4) isolated from the fungus Lactarius vellerus was converted into velleral (5), also by human saliva.

Two novel bis(bibenzyls) named paleatins A (1) and B (2) have been isolated from the liverwort, Marchantia paleacea var. diptera. Their structures have been establishied by a combination of high-resolution NMR spectra and chemical degradation. A total synthesis of paleatin A has been accomplished in ten steps.

A novel binaphthyl (1) and three novel benzophenone derivatives (2-4) have been isolated from the fungus (Ascomycetes) Daldinia concentrica. Their structures have been established by a combination of high resolution NMR spectra, X-ray crystallographic analysis and chemical degradation. Compounds 2 and 3 possess plant-growth inhibitory activity.

A novel ent-kaurane diterpenoid, ent-1alpha-acetoxy-7beta,14alpha-dihydroxy-kaur-16-en-15-on has been isolated from leaves of Croton tonkinensis GAGNEP. Its structure was determined by a combination of spectroscopy, X-ray crystallographic analysis and the chemical reaction acetylation.

A novel type bisacridone alkaloid, named citbismine-A, was isolated from the roots of Marsh grapefruit; its structure was elucidated by spectroscopic method and unequivocally by X-ray crystal analysis as 1

Reduction of 16-anhydrogitoxigenin 3-acetate (II) with NaBH4-transition metal chloride systems as well as with transition metal hydrides gave geometrically isomeric card-17 (20)-enolides, V and VI, new type of cardenolide. Stereochemistry of the products was discussed on the basis of Cotton effect, 1H-and 13C-nuclear magnetic resonance spectra. The structure and ratio of the products varied depending on the kind of transition elements.

Five new diarylheptanoids, yashabushidiol A and B, yashabushiketodiol A and B, and yashabushitriol, have been isolated from the male flowers of Alnus sieboldiana MATSUM. and their absolute structures determined by spectral methods and chemical transformations to known yashabushiketol and dihydroyashabushiketol.

The product (III) was obtained by Diels-Alder reaction of 16, 17-dehydrodigitoxigenin 3-acetate (I) with ethyl acrylate on heating. The structure of III was determined by X-ray analysis, and III was found to be a head to head adduct of ethyl acrylate on the β-side of the 16, 20 (22)-diene moiety of I. The analogous reaction of I with dimethyl maleate gave two products (VI and VII) in similar yields. The structure of VI was also determined by X-ray analysis, and VII was considered to be the 24-epimer of VI, based on the spectral data and interconversion between VI and VII upon alumina treatment. In VI and VII, the double bond was found to be shifted towards the conjugated position from the original position in the diene synthetic product. Dimethyl fumarate gave a normal product (X) on addition to I on the β-side of the diene system. Upon alumina treatment, X was transformed into VI and VII, confirming the structures of VII and X. By analogy with the β-side addition of the above dienophiles, the configurations of 16-H and 22-H of the dimer (II) were both proposed to be α.

Along with the known hydrangenosides C and D, new glucosides of the same series, hydrangenosides E, F, and G, have been isolated from Hydrangea scandens and their absolute structures have been established. These glucosides were found to consist of secologanin and a shikimate-malonate derived C-13 unit. Hydrangenoside G is considered to be a biogenetic intermediate of the other glucosides.

Along with the known hydrangenoside A (4), new glucosides of the same series, hydrangenosides B (1), C (2) and D (3), have been isolated from Hydrangea macrophylla and their absolute structures have been established. These substances are considered to be formed by an aldol-type condensation of secologanin (5) with a shikimate-malonate derived moiety followed by decarboxylation. Hydrangenoside A (4) and B (1) are stereoisomers, while hydrangenoside C (2) and D (3) are their homologues containing one fewer acetate unit and also are stereoisomers.

Two novel alkaloids, leucotamine (1) and O-methylleucotamine (2), with a 3R-hydroxybutyryl group, and another new alkaloid, 3-O-acetylungiminorine (3), were isolated from leaves of Leucojum asetivum (Amaryllidaceae) together with five known alkaloids. O-Methylleucotamine (2) and 3-O-acetylungiminorine (3), as well as four known bases, were also isolated from bulbs of this plant. The stereochemistries of the new compounds 1, 2 and 3 were established on the basis of chemical and spectral data.

The structure of deoxytazettine neomethine (I), derived from tazettine (III) via 5 steps, was confirmed by synthesis of its optically active and racemic forms. A key step in the synthesis, conversion of 2'-bromomethyl-4', 5'-methylenedioxy-2-biphenylcarbal-dehyde (VI) to 7-cyano-5, 7-dihydro-2, 3-methylenedioxydibenz [c, e] oxepin (VII), was achieved by employing a novel method which had been developed for synthesis of 5-cyano-5, 7-dihydrodibenz [c, e] oxepin (V). The nuclear magnetic resonance spectra of the neomethine (I) and its synthetic intermediates were discussed.

β-Galactosidase obtained from Aspergillus oryzae was found to have strong transglycosylation activity. The glycosylation of water-soluble and insoluble alcohols was successfully performed under mild conditions (pH 5 at 4-37°C) with this enzyme. The enzyme was also applied to the onestep synthesis of several cardiac glycosides that are diffcult to obtain by ordinary chemical methods.

The bulbs of Zephyranthes carinata HERB. (Amaryllidaceae) were found to contain pretazettine (I) and a new phenolic base, carinatine (II), as well as lycorine (III), galanthine (IV), and haemanthamine (V). Carinatine (II), C17H21NO4■, was established to be O-demethylgalanthine.

Dimerization of 16, 17-dehydrodigitoxigenin 3-acetate (I) and its 21R-and 21S-ethoxy derivatives (II and III) was found to occur on heating the monomers in toluene. This dimerization appeared to take place between the 16, 20 (22)-diene system of one monomer and the 16, 17-double bond of another monomer by a Diels-Alder type reaction, giving the dimers IV, V, and VI, respectively. Ultraviolet irradiation of a chloroform solution of II also gave the dimer V, but UV irradiation of I and III was ineffective. The structures of these dimers were established on the basis of their molecular weights, spectral data, and the properties of their dianhydro derivatives.

Treatment of 16β, 17β-epoxy-17α-digitoxigenin 3-acetate (V), which is readily available from gitoxigenin (Ib), with dilute alkali in absolute ethanol gave 16, 17-dehydro-21R-ethoxydigitoxigenin 3-acetate (VIII) and 21S-epimer (IX). Catalytic hydrogenation of VIII and IX gave stereospecifically 21R-ethoxydigitoxigenin 3-acetate (X) and 21S-ethoxy-17α-digitoxigenin 3-acetate (XI), respectively. Further reduction of X and XI with NaBH4 effectively eliminated ethoxy group to afford digitoxigenin 3-acetate (IVb) and 17α-epimer (III), respectively. By the sequence of these reactions, chemical transformation of gitoxigenin (Ib) to digitoxigenin 3-acetate (IVb) was achieved in fair yield.