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The asymmetric total synthesis of toxicodenane A, a sesquiterpenoid expected to be promising for diabetic nephropathy, was achieved. In the synthesis, a samarium iodide (SmI

Feroniellin analogs isolated from Feroniella lucida possess a furanocoumarin skeleton connected to monoterpenic five- to seven-membered ethereal rings by an ether linkage and exhibit a broad spectrum of biological activities. In this contribution, we intended to establish a "ring-size-divergent" synthetic strategy for the monoterpenic five- to seven-membered ethereal rings through the chemical sythesis of feroniellins. The short and comprehensive synthesis of feroniellins was achieved in only two steps from easily available bergamottin based on the "ring-size-divergent" strategy. In addition, these syntheses resulted in revision of the proposed structures for feroniellins A and B and the determination of all the absolute configurations of feroniellins; their preliminary anti-inflammatory activities were investigated as well.

In this contribution, we propose a new synthetic approach to tetrodotoxin (TTX), one of the most famous marine toxins that, after first preparing a functionalized linear substrate, forms a cyclohexane core from the substrate utilizing our mercuric triflate (Hg(OTf)2)-catalyzed cycloisomerization reaction. The concept was applied to the synthesis of 11-nor-6,7,8-trideoxyTTX and 11-nor-4,9-anhydro-6,7,8-trideoxyTTX, which are unnatural TTX analogues, demonstrating the validity of our new approach.

Bone loss and bone-related disease are associated with the deregulation of osteoclast function, and therefore agents that affect osteoclastogenesis have attracted attention. The purpose of the present study was to discover modified kavalactone analogs as potential anti-osteoclastogenic agents. We assessed the effect of 26 analogs on osteoclast differentiation in vitro. The most potent compound, (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22), suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of RAW264 cells with IC50 values of 4.3 µM. A partial structure-activity relationship study revealed the importance of fluorine and its position within the 5,6-dehydrokawain skeleton. The results of a pit formation assay suggested that compound 22 prevents osteoclastic bone resorption by inhibiting osteoclastogenesis. Moreover, compound 22 downregulated mRNA expression levels of RANKL-induced nuclear factor of activated T cells c1 (NFATc1) and osteoclastogenesis-related genes. These results suggest that (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one scaffold could lead to the identification of new anti-resorptive agents.

There are marine cytotoxic bromotriterpenoids, named the thyrsiferol family that are structurally characterized by some tetrahydropyran (THP) and tetrahydrofuran (THF) rings. The thyrsiferol family belongs to natural products that are often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic tetrasubstituted carbon centers. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, to elucidate ambiguous stereostructures and unassigned absolute configurations of aplysiol B, laurenmariannol, and saiyacenol A, members of the thyrsiferol family, we carried out their asymmetric chemical syntheses featuring 6-exo and 5-exo oxacyclizations of epoxy alcohol precursors and 6-endo bromoetherification of a bishomoallylic alcohol. In this paper, we report total assignments of their stereostructures through their asymmetric chemical syntheses and also their preliminary cytotoxic activities against some tumor cells. These results could not have been achieved without depending on asymmetric total synthesis.

Anti-inflammatory activity of aculeatin and toddaculin, which are coumarins with a similar structure isolated from Toddalia asiatica (L.) LAM., was evaluated using lipopolysaccharide (LPS)-stimulated RAW264 mouse macrophage cells. Both aculeatin and toddaculin significantly inhibited mRNA expression of inflammatory mediators and nitric oxide production. Furthermore, Toddaculin suppressed LPS-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 and inhibited LPS-induced activation of nuclear factor-kappaB (NF-κB). However, aculeatin did not exhibit such effects, suggesting that aculeatin and toddaculin suppress LPS-induced inflammation of RAW264 cells via different mechanisms. The cellular uptake of these compounds was also evaluated. Toddaculin was detected in RAW264 cells after 4 and 24 h. However, aculeatin levels were not observed in RAW264 cells at all incubation intervals. These results indicate that de-epoxidation of a prenyl group can increase hydrophobicity of molecule and is thought to accelerate cellular uptake and/or interactions with the phospholipid bilayers of cell membranes.

The efficient formal total synthesis of histrionicotoxin alkaloids was achieved. In this process, two key reactions were used to construct a core 1-azaspiro[5.5]undecane framework common to histrionicotoxins: a mercuric triflate (Hg(OTf)2)-catalyzed cycloisomerization of a linear substrate, which was developed in our laboratory, and a samarium iodide (SmI2)-mediated ring expansion.

Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent.

Anti-inflammatory activity of aculeatin and toddaculin, which are coumarins with a similar structure isolated from Toddalia asiatica (L.) LAM., was evaluated using lipopolysaccharide (LPS)-stimulated RAW264 mouse macrophage cells. Both aculeatin and toddaculin significantly inhibited mRNA expression of inflammatory mediators and nitric oxide production. Furthermore, Toddaculin suppressed LPS-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 and inhibited LPS-induced activation of nuclear factor-kappaB (NF-κB). However, aculeatin did not exhibit such effects, suggesting that aculeatin and toddaculin suppress LPS-induced inflammation of RAW264 cells via different mechanisms. The cellular uptake of these compounds was also evaluated. Toddaculin was detected in RAW264 cells after 4 and 24 h. However, aculeatin levels were not observed in RAW264 cells at all incubation intervals. These results indicate that de-epoxidation of a prenyl group can increase hydrophobicity of molecule and is thought to accelerate cellular uptake and/or interactions with the phospholipid bilayers of cell membranes.

The effect of temperature on the static tensile properties of the metastable austenitic steel JIS-SUS304 was investigated to clarify the conditions of stress-induced martensitic transformation behavior for maximum uniform elongation. Results of the static tensile tests showed that the tensile strength increased with decreasing temperature and that uniform elongation reached a maximum value at 308 K. The inverse temperature dependence of 0.2% proof stress was observed below 243 K. The volume fraction of martensite increased with decreasing deformation temperature. The conditions under which the stress-induced transformation resulted in the maximum uniform elongation due to the transformation-induced plasticity (TRIP) effect in SUS304 steel were summarized in terms of the martensite volume fraction and rate of transformation. The martensite volume fraction at true strain, which indicates the maximum transformation rate, was found to be approximately 35% independent of the deformation temperature. In stress–strain relationships for which the maximum uniform elongation was obtained, both the evolution rate of the dislocation density and the work-hardening continued to increase until near-uniform elongation was observed, and the maximum calculated value of work-hardening was almost 20 MPa/%.

著者らは地震波形の収集が困難な自治体観測点を対象に，最大地動加速度と計測震度の地盤増幅度からサイト特性を推定する手法を提案している．この手法はサイト特性の周期0.1～1秒における任意区間の平均増幅度は精度良く推定できたが，周期1～2秒では推定精度が良くなかった．本研究では周期1～2秒のサイト特性の推定精度を向上させるために，地震動の周期1～2秒成分の相対的な強さと相関がある最大加速度比をサイト特性推定の際に考慮した．推定にあたり，M7前後の地震観測記録から計算した最大加速度比とサイト特性の周期1～2秒の増幅度の相関を調べたところ，両者に良好な相関が見られた．地盤増幅度と最大加速度比をパラメータとする式によってサイト特性を求めたところ，周期1～2秒におけるサイト特性の観測値と推定値の相関係数が向上した．また，ほとんどの周期帯で相関係数が0.9を超えていた．

We studied the bioactivities of constituents from two tropical medicinal plants, Cunila spicata and Hyptis fasciculata. These plants found in Brazil belong to the Labiatae family. Four known compounds obtained from these herbs were identified as 3alpha, 24-dihydoxylurs-12-en-28-oic acid, betulinic acid, aurantiamide acetate, and aurantiamide benzoate by spectroscopic means. 3alpha, 24-Dihydoxylurs-12-en-28-oic acid has potent inhibitory activity against Streptococcus salivarius, Streptococcus pneumoniae, Streptococcus pyogenes, and Porphyromomas gingivalis. Aurantiamide benzoate exhibited moderate inhibitory activity against xanthine oxidase. It was clarified that herbs Cunila spicata and Hyptis fasciculata are effective against bronchitis and gout.

Two known flavonoids were isolated from a tropical medicinal plant, Hyptis fasciculata (Labiatae), found in Brazil. Flavonoids were identified as cirsilineol (1) and cirsimaritin (2) by spectroscopic means and were exhibited potent antibacterial activity against Helicobacter pylori, and cirsilineol (1) had weak antibacterial activity against Escherichia coli and Salmonella enteritidis. Following up on the relationship between anti-H. pylori activity and flavonoids with methoxy groups, several methoxy flavonoids were evaluated for proliferation of H. pylori.

From the “ Evolutive Model of the Domanial Regime” to the “ Virtues of Comparatism”. Some Introductory Remarks. Aiming to complete the general introduction to the symposium, the author first underlines that the most important progress in the rural history of the Early Middle Age is the reduced dichotomy between the manorial model and the allodial model through the researches led in the spirit of dialog. He next indicates that Adriaan Verhulst’s paper in Spoleto, through the ways by which he traced the evolution of the early medieval economy, had already prepared the field for this effect. Then the author explains his experiences in comparative history as a Japanese historian, in order to fortify the comparative method underpinning the symposium. The article ends by stressing the necessity of considering the geographical framework of the comparison in the medieval rural history.

Morimoto Yoshiki. Le commentaire de Césaire (1222) sur le polyptyque de Prüm (893). Données pour le IXe ou le XIIIe siècle ?. In: Revue belge de philologie et d'histoire, tome 68, fasc. 2, 1990. Histoire - Geschiedenis. pp. 261-290.

[structure: see text] The first asymmetric total synthesis of a structurally novel cis-cyclopent[c]isoxazolidine alkaloid, (-)-pyrinodemin A (3), which exhibits potent cytotoxicity, has been accomplished through a highly diastereoselective intramolecular nitrone-olefin cycloaddition reaction as the key step. Thus, it has been found that the hitherto unknown absolute configuration of pyrinodemin A is as indicated in the structural formula 3.

In this review article, we report our recent contributions to the total synthesis of the highly symmetric squalene-derived cytotoxic triterpene polyethers, teurilene (3), (+) -14-deacetyl eurylene (1), (+) -eurylene (4), (-) -glabrescol (5), and (-) -longilene peroxide (2), based on the concept of two-directional synthesis utilizing their intrinsic molecular symmetry as the fundamental strategy. In the course of these synthetic studies, syn oxidative cyclizations of bishomoallylic tertiary alcohols promoted by rhenium (VII) oxide have been accomplished with excellent diastereoselectivities. The critical trans or cis selectivity between the 2- and 5-positions of the tetrahydrofuran (THF) ring in the products has been observed, depending on the substrates employed. In addition, the meso structure 6 originally proposed by Jacobs et al. has been revised to the optically pure C2 symmetric structure 5 through its enantioselective total synthesis. Furthermore, the unknown absolute configuration of longilene peroxide has been determined by this synthesis as shown in the structural formula 2.

Morimoto Yoshiki. Réflexions d'un historien japonais sur le livre de Guy Bois. In: Médiévales, n°21, 1991. L'an Mil. Rythmes et acteurs d'une croissance, sous la direction de Monique Bourin . pp. 63-68.

Further investigations of the secondary metabolites of a gorgonian Briareum sp., collected at Amami Oshima, Kagoshima Prefecture, have yielded 10 new briarane diterpenes, briarlides I-R (1-10). The structures were elucidated on the basis of spectral analysis.