Isolation of C-29 oxygenated oleanane triterpenoids and a (+)-muurolene type sesquiterpenoid from the fruiting bodies of Fuscoporia torulosa and their bioactivities.

Basidiomycetes with a wide variety of skeletons of secondary metabolites can be expected to be the source of new interesting biological compounds. During our research on basidiomycetes, two new C-29 oxygenated oleanane-type triterpenes (1 and 2) and torulosacid (3), a muurolene type sesquiterpenoid with a five-membered ether ring along with nine known compounds (4-12), were isolated from the MeOH extract of the fruiting bodies of Fuscoporia torulosa. The structures of 1-3 were determined by NMR and HREIMS analysis. Further studies on the stereochemistry of 3 were conducted using X-ray crystallographic analysis and comparison of experimental and calculated ECD spectra. In the antimicrobial assay of isolates, 1, 7, and 9 showed growth inhibitory activity against methicillin-resistant Staphylococcus aureus and other gram-positive strains. Isolation of oleanane type triterpenes from fungi including basidiomycetes, is a unique report that could lead to further isolation of new compounds and the discovery of unique biosynthetic enzymes.

Synthesis of a Cyclic Dinucleotide Analogue with Ambiguous Bases, 5-Aminoimidazole-4-carboxamide.

Cyclic dinucleotides (CDNs) are second messengers composed of two purine nucleotides. In recent years, the structural diversity of CDNs and their functionality in biological processes are being intensely studied. Herein we report the chemical synthesis of cyclic di-5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranosyl monophosphate (c-di-ZMP) (1), which consists of two 5-amino-4-imidazolecarboxamide ribonucleotides (Z-ribonucleotides) linked via two phosphodiester linkages. Construction of the CDN skeleton with an N1-dinitrophenylhypoxanthine base (HxaDNP-base) by phosphoramidite chemistry and the subsequent ring-opening reaction of HxaDNP-base successfully yielded the desired 1.

Eremophilanes from Ligularia hookeri Collected in China and Structural Revision of 3ß-Acyloxyfuranoeremophilan-15,6-olide.

Chemical constituents of Ligularia hookeri (Asteraceae) collected in Yunnan and Sichuan Provinces in China were examined for the first time. Seven furanoeremophilanes, five of which were new, as well as known bisabolane- and eudesmane-type sesquiterpenoids, were isolated. Spectroscopic evidence indicates that the previously reported 3ß-(2'-methylpropenoyloxy)furanoeremophilan-15,6ß-olide should be revised to 3ß-(2'-methylpropenoyloxy)furanoeremophilan-15,6α-olide.

Structure Determination of an Ag(I) -Mediated Cytosine-Cytosine Base Pair within DNA Duplex in Solution with (1) H/(15) N/(109) Ag NMR Spectroscopy.

The structure of an Ag(I) -mediated cytosine-cytosine base pair, C-Ag(I) -C, was determined with NMR spectroscopy in solution. The observation of 1-bond (15) N-(109) Ag J-coupling ((1) J((15) N,(109) Ag): 83 and 84 Hz) recorded within the C-Ag(I) -C base pair evidenced the N3-Ag(I) -N3 linkage in C-Ag(I) -C. The triplet resonances of the N4 atoms in C-Ag(I) -C demonstrated that each exocyclic N4 atom exists as an amino group (-NH2 ), and any isomerization and/or N4-Ag(I) bonding can be excluded. The 3D structure of Ag(I) -DNA complex determined with NOEs was classified as a B-form conformation with a notable propeller twist of C-Ag(I) -C (-18.3±3.0°). The (109) Ag NMR chemical shift of C-Ag(I) -C was recorded for cytidine/Ag(I) complex (δ((109) Ag): 442 ppm) to completed full NMR characterization of the metal linkage. The structural interpretation of NMR data with quantum mechanical calculations corroborated the structure of the C-Ag(I) -C base pair.

Diversity in Chemical Constituents of Ligularia longihastata Collected in China.

Root constituents of Ligularia longihastata were examined for the first time. Fourteen eremophilane sesquiterpenes, including two new eremophilanes identified as 3α-isobutyroyloxy-7ßH-eremophila-9,11-dien-8-one and 3ß-angeloyloxy-1ß,10ß-epoxyfuranoeremophilan-9-one, and three eudesmanes were isolated. From samples collected in Baiyu County, Sichuan Province, furanoeremophilane derivatives were isolated, while various eremophilan-8-ones were isolated from samples collected in Kangding County, Sichuan. The results suggest chemical diversity in the species.

Chemical Constituents of Ligularia wilsoniana Collected in Chongqing, China.

The chemical constituents of Ligularia wilsoniana were studied for the first time, using four samples collected in Chongqing City, China. Two new compounds, 6ß-(2',3'-epoxy-2'-methylpropanoyloxy)-ß,10ß-epoxyfuranoeremophilane and 11αH-6ß-(2'-hydroxymethylacryloyloxy)-1ß,10ß;7ß,8ß- diepoxyeremophilanolide, as well as eight known compounds, were isolated from one of the samples, while three to four known furanoeremophilanes were isolated from the other three samples. No compound was common to the two classes of the samples, demonstrating the presence of at least two chemotypes of this species.

Macrocyclization Using RCM Reactions. Synthesis of Simple Metacyclophanes and Synthetic Efforts Toward Platycarynol, a 15-Membered Aromatic Ether.

- Preparation of 13- to 19-membered carbocycles (metacyclophanes) from 1,3-disubstituted benzene derivatives has been successfully carried out using the RCM reaction, but similar starting materials having diphenyl ether did not cyclize to 15-membered compounds, whose ground state conformations were calculated and discussed. Several attempts to cyclize to form platycarynol are described.

Constituents of Ligularia brassicoides Collected in China: A New Diels-Alder Adduct of Eremophilan-10ß-ol and Methacrylic Acid.

Chemical study of four samples of Ligularia brassicoides collected in Sichuan Province of China afforded 18 compounds, five of which were new. LC-MS profiles were somehow similar to each other, although the compound ratio was slightly different. One of the new compound was a Diels-Alder adduct between franoeremophilan-10ß-ol and methacrylic acid.

Four New Sesquiterpenoids from Ligularia subspicata Collected in China; Isolation of a Bakkane-type Lactone, an Eremophilane-type Lactone, and Two Ortho Esters.

A bakkane type lactone, an eremophilane type lactone, and two ortho esters were isolated from Ligularia subspicata collected in Sichuan Province, China. The ortho ester type compound has been isolated from Ligularia for the first time.

Synthesis of chiral hexasubstituted cyclohexanediol, a key intermediate for the synthesis of verticillol, from (+)-dihydrocarvone; attempted cyclization to 12-membered carbocycle in verticillol using RCM reaction.

A cyclohexane derivative with three chiral centers, a key intermediate for the synthesis of a diterpene verticillol, was prepared starting from (+)-dihydrocarvone. A further challenge to cyclize to a 12-membered carbocycle was attempted, although the products were dimeric derivatives presumably due to an undesirable conformation of the substrate.

Synthesis of a key intermediate, 10-acetyl-7-(t-butyldiphenylsilyloxymethyl)-4-methylbicyclo[5.3.0]dec-4-en-1-ol, in the synthesis of pseudolaric acid A.

10-Acetyl-7-(t-butyldiphenylsilyloxymethyl)-4-methylbicyclo[5.3.0]dec-4-en-1-ol was synthesized by aldol cyclization to a five-membered ring, epoxidation, samarium diiodide-induced ring opening, and the RCM reaction to the seven-membered carbocycle. This method has succeeded in constructing the desired stereochemistry in the synthesis of pseudolaric acid A.

Use of RCM reactions for construction of eight-membered carbocycles and introduction of a hydroxy group at the juncture between five- and eight-membered carbocycles.

Model studies for total synthesis of YW3699 were carried out in order to introduce a hydroxy group at the ring juncture between 5- and 8-membered carbocycles. The five-membered ring part, hydrazone, and aldehyde with a cyclohexane ring were connected by the Shapiro reaction, followed by conversion to diketones, which were treated with IBX to afford hydroxylated models.

Synthesis of a hydrindenone in rings C and D of YW3699.

A hydrindenone in rings C and D of YW3699 was synthesized starting from (-)-isocarvone. The stereochemical requirement in this ring was successfully achieved by Eschenmoser-Claisen rearrangement followed by alkylation and the aldol reaction to afford the desired hydrindenone, which can be used for further elaboration of YW3699.

Antioxidation mechanism studies of caffeic acid: identification of antioxidation products of methyl caffeate from lipid oxidation.

As a part of a research project on the elucidation of the chain-breaking antioxidation mechanism of natural phenols in food components, caffeic acid, a polyphenolic acid widely distributed in edible plants, was investigated. The identification and time course analysis of the antioxidation reaction products from methyl caffeate were carried out in the ethyl linoleate oxidation system. The antioxidation reaction produced a quinone derivative of methyl caffeate as an antioxidation product during the initial stage, which was identified by (13)C NMR. The quinone, however, was not the final product, and a further reaction occurred to produce several new peroxides. The isolation and structure determination of the peroxides revealed that they had tricyclic structures, which consisted of ethyl linoleate, methyl caffeate, and molecular oxygen. On the basis of the formation pathway of these products, an antioxidation reaction mechanism of methyl caffeate, including the redox reaction of the caffeate and Diels-Alder reaction of the produced peroxides, was proposed.

Sesquiterpenoids isolated from Eupatorium glehnii. Isolation of guaiaglehnin A, structure revision of Hiyodorilactone B, and genetic comparison.

A new sesquiterpenoid substituted with unsaturated ester, guaiaglehnin A (1), along with 15 previously known compounds, were isolated from the methanol extract of the terrestrial part of Eupatorium glehnii (Compositae) collected in Nagano Prefecture, Japan, the results of which supported the previous study by Takahashi et al. The chemical constituents of E. glehnii collected in Nagano Prefecture and those collected in Tokushima or Hokkaido are quite different, depending on collection site, although the species are identical. The base sequences of three different samples were identical. Diversity in the chemical components was detected, though no diversity existed in the DNA sequence. In this study, eupasimplicin A (2) was also isolated, whose presence in the extract of E. chinense simplicifolium was recorded but not in an article. The side chain geometry of hiyodorilactone B (5) was revised to be E.

Chemical and genetic diversity of Ligularia vellerea in Yunnan, China.

Intra-specific diversity in Liularia vellerea growing in the northwestern to central Yunnan province of China was studied by chemical and genetic approaches. Samples collected in the Jianchuan, Lijiang, and Zhongdian areas contained 6,15-dioxygenated furanoeremophilanes as their major components (type A); whereas samples from the Luguhu area accumulated 1,6-dioxygenated furanoeremophilanes (type B); a sample from near Kunming, however, contained 6,15-dioxygenated eremophilanolides (type C). 11 beta H- and 11 alpha H-6 beta-angeloyloxy-15-carboxyeremophil-7-en-12,8-olides (eremofarfugins D and E) were also isolated and their structures were determined. A correlation between the composition and the DNA sequence was observed in the ITSs.

Isomerization reactions of allylic alcohols into ketones with the Grubbs reagent.

Allylic alcohols were isomerized into ketones by the action of the Grubbs reagent. Some model alcohols were prepared and tested under similar conditions to reveal that less substituted alkenes rearrange more easily. More hindered alcohols are stable under these conditions, however, the simple allylic alcohols tend to isomerize producing ethyl ketone and the corresponding degraded methyl ketone.

Seven germacranolides, eupaglehnins A, B, C, D, E, and F, and 2alpha-acetoxyepitulipinolide from Eupatorium glehni.

Four new germacrane-type sesquiterpenoids with unsaturated acids as esters at the 8-position, two chlorine atom-containing lactones, 2alpha-acetoxyepitulipinolide, and 12 previously known compounds have been isolated from the MeOH extract of Eupatorium glehni (Compositae) and their structures have been determined on the basis of spectral data analyses.

Total synthesis and absolute configuration of liverwort diterpenes, (-)-13(15)E,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene and (-)-13(15)Z,16E-3beta,4beta-Epoxy-18-hydroxysphenoloba-13(15),16-diene, by use of the ring closing metathesis reaction applied to seven-membered carbocycles with a trisubstituted double bond.

Seven-membered cyclic compounds possessing trisubstituted double bonds have been effectively constructed employing the Grubbs catalyst to effect olefin metathesis. The keto ester does not undergo cyclization; however, alcohols protected by the silyl groups smoothly cyclized into seven-membered compounds. The product was successfully converted to (-)-13(15)E,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene and (-)-13(15)Z,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene, liverwort diterpenes isolated from Anastrophyllum auritum to establish the absolute configuration.