Anti-inflammatory diterpenoids from the brown alga Dictyota coriacea.

A new xenicane diterpene named 4α-acetoxyisodictyohemiacetal (1) was isolated from the brown alga Dictyota coriacea, along with 11 known diterpenoids. The structure of 1 was established by spectroscopic analyses, and its absolute configuration was determined by comparing the experimental and theoretical electronic circular dichroism (ECD) spectra. Two dictyodiacetal diastereomers (5 and 6) were isolated and the full NMR assignments were performed.

A nitrogenase-like enzyme is involved in the novel anaerobic assimilation pathway of a sulfonate, isethionate, in the photosynthetic bacterium .

Prokaryotes contribute to the global sulfur cycle by using diverse sulfur compounds as sulfur sources or electron acceptors. In this study, we report that a nitrogenase-like enzyme (NFL) and a radical SAM enzyme (RSE) are involved in the novel anaerobic assimilation pathway of a sulfonate, isethionate, in the photosynthetic bacterium . The genes for NFL are localized at a locus containing genes for known sulfonate metabolism in the genome.

Structure-activity relationship of anti-inflammatory meroterpenoids isolated from Dictyopteris polypodioides in RAW264 cells.

In this study, we explored anti-inflammatory compounds from the brown alga Dictyopteris polypodioides and isolated 7 meroterpenoids. Their anti-inflammatory activities were evaluated using the lipopolysaccharide-stimulated mouse macrophage cell line, RAW264. Yahazunol (1) exhibited similar nitric oxide (NO) production inhibitory activity as zonarol (2), which has previously been shown to be an anti-inflammatory compound.

Divergent Nine-Step Syntheses of Perhydrohistrionicotoxin Analogs and Their Inhibition Activity Toward Chicken α4β2-Neuronal Nicotinic Acetylcholine Receptors.

Histrionicotoxin (HTX) alkaloids, which are isolated from Colombian poison dart frogs, are analgesic neurotoxins that modulate nicotinic acetylcholine receptors (nAChRs) as antagonists. Perhydrohistrionicotoxin (pHTX) is the potent synthetic analogue of HTX and possesses a 1-azaspiro[5.5]undecane skeleton common to the HTX family.

Establishment of "Ring-Size-Divergent" Synthetic Strategy: Divergent Synthesis, Stereochemical Assignments, and Biological Activity Studies of Nerolidol-Type Sesquiterpenoids and Feroniellins.

Biomimetic epoxide-opening cascade cyclizations of polyepoxides enable the efficient and rapid construction of polyether skeletons. In this study, we discovered a method for switching the cyclization mode from tetrahydrofuran to tetrahydropyran (THP) formation in epoxide-opening cascades of polyepoxides. The THP formation proceeded via an epoxonium-ion intermediate by simple heating in neutral water.

Dose-dependent alkaloid sequestration and N-methylation of decahydroquinoline in poison frogs.

Sequestration of chemical defenses from dietary sources is dependent on the availability of compounds in the environment and the mechanism of sequestration. Previous experiments have shown that sequestration efficiency varies among alkaloids in poison frogs, but little is known about the underlying mechanism. The aim of this study was to quantify the extent to which alkaloid sequestration and modification are dependent on alkaloid availability and/or sequestration mechanism.

Asymmetric Total Synthesis of Toxicodenane A by Samarium-Iodide-Induced Barbier-Type Cyclization and Its Cell-Protective Effect against Lipotoxicity.

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)-induced Barbier-type cyclization and a regio- and stereoselective allylic oxidation followed by a dehydration cyclization were employed as key steps. Furthermore, the first asymmetric syntheses of both enantiomers were accomplished using the previously mentioned synthetic strategy.

Asymmetric Total Syntheses, Stereostructures, and Cytotoxicities of Marine Bromotriterpenoids Aplysiol B (Laurenmariannol) and Saiyacenol A.

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.

Establishing a "Ring-Size-Divergent" Synthetic Strategy: Synthesis, Structural Revision, and Absolute Configuration of Feroniellins.

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.

One-Step Synthesis of the 1-Azaspiro[5.5]undecane Skeleton Characteristic of Histrionicotoxin Alkaloids from Linear Substrates via Hg(OTf) -Catalyzed Cycloisomerization.

Histrionicotoxin (HTX) alkaloids isolated from the poison arrow frogs possess a unique structure characterized by a 1-azaspiro[5.5]undecane skeleton common to the HTX family. The unique molecular architecture of HTXs and the interest as potential target drugs have prompted synthetic chemists to promote the total synthesis so far.

Tetrodotoxin Framework Construction from Linear Substrates Utilizing a Hg(OTf)-Catalyzed Cycloisomerization Reaction: Synthesis of the Unnatural Analogue 11--6,7,8-Trideoxytetrodotoxin.

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))-catalyzed cycloisomerization reaction. The concept was applied to the synthesis of 11--6,7,8-trideoxyTTX and 11--4,9-anhydro-6,7,8-trideoxyTTX, which are unnatural TTX analogues, demonstrating the validity of our new approach.

4β-Hydroxywithanolide E and withanolide E from Physalis peruviana L. inhibit adipocyte differentiation of 3T3-L1 cells through modulation of mitotic clonal expansion.

Obesity is a risk factor for many diseases, including type 2 diabetes and cardiovascular disease, and is related to the rising morbidity and mortality. Discovery of agents targeting adipogenesis, especially from natural sources, is important for the treatment of obesity. Here, we aimed to identify anti-adipogenic substances in methanol extracts of Physalis peruviana and to investigate their effect, along with underlying mechanisms.

Use of whole-body cryosectioning and desorption electrospray ionization mass spectrometry imaging to visualize alkaloid distribution in poison frogs.

Ambient mass spectrometry is useful for analyzing compounds that would be affected by other chemical procedures. Poison frogs are known to sequester alkaloids from their diet, but the sequestration pathway is unknown. Here, we describe methods for whole-body cryosectioning of frogs and use desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to map the orally administered alkaloid histrionicotoxin 235A in a whole-body section of the poison frog Dendrobates tinctorius.

Fluorinated Kavalactone Inhibited RANKL-Induced Osteoclast Differentiation of RAW264 Cells.

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.

Formal total synthesis of histrionicotoxin alkaloids Hg(OTf)-catalyzed cycloisomerization and SmI-induced ring expansion.

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))-catalyzed cycloisomerization of a linear substrate, which was developed in our laboratory, and a samarium iodide (SmI)-mediated ring expansion.

Evaluation of Aculeatin and Toddaculin Isolated from Toddalia asiatica as Anti-inflammatory Agents in LPS-Stimulated RAW264 Macrophages.

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.

Total Syntheses of Lepadiformine Marine Alkaloids with Enantiodivergency, Utilizing Hg(OTf) -Catalyzed Cycloisomerization Reaction and their Cytotoxic Activities.

The enantioselective total syntheses of lepadiformine marine alkaloids, azatricyclic natural products isolated from marine tunicates, were completed. These alkaloids have a unique chemical structure characterized by the trans-1-azadecalin (AB ring system) fused with the spirocyclic ring (AC ring system). Here we found that a cycloisomerization reaction from functionalized linear substrates to a 1-azaspiro[4.

Synthesis of novel 5,6-dehydrokawain analogs as osteogenic inducers and their action mechanisms.

An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs.

Total Synthesis of the Cytotoxic Marine Triterpenoid Isodehydrothyrsiferol Reveals Partial Enantiodivergency in the Thyrsiferol Family of Natural Products.

Recently, the phenomenon of enantiodivergence was uncovered as a new phenomenon in the biosynthesis of natural products. In nature, chiral natural products are usually produced in optically active form, but both enantiomers sometimes arise in different genera and/or species or in a single species. Here we show through enantioselective total synthesis that the natural product isodehydrothyrsiferol shows partial enantiodivergency in that six of the nine or ten asymmetric centers are enantiomeric to those of other members of the marine squalene-derived triterpenoid thyrsiferol family.

5,6-Dehydrokawain from Alpinia zerumbet promotes osteoblastic MC3T3-E1 cell differentiation.

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.

Total Synthesis of (-)-Lepadiformine A Utilizing Hg(OTf)2-Catalyzed Cycloisomerization Reaction.

A cytotoxic marine alkaloid (-)-lepadiformine A (1) possesses a unique structure characterized by the trans-1-azadecalin AB ring system fused with the AC spiro-cyclic ring. In this research, we found that a cycloisomerization reaction from amino ynone 2 to a 1-azaspiro[4.5]decane skeleton 3, corresponding to the AC ring system of 1, is promoted by Hg(OTf)(2).

Biomimetic epoxide-opening cascades of oxasqualenoids triggered by hydrolysis of the terminal epoxide.

The biomimetic epoxide-opening cascades from squalene polyepoxides 4-6 to triterpene polyethers (oxasqualenoids) teurilene (1), glabrescol (2), and omaezakianol (3), respectively, were reproduced in a single event by chemical reaction. These cascades proceeded through the 5-exo tandem cyclization triggered by Brønsted acid-catalyzed hydrolysis of the terminal epoxide, mimicking the direct hydrolysis mechanism of epoxide hydrolases.

Rings D-seco and B,D-seco tetranortriterpenoids from root bark of Entandrophragma angolense.

Investigation of the root bark extract of Entandrophragma angolense led to identification of two gedunin-type limonoids 5-hydroxy-7-deacetoxy-7-oxogedunin and 5,6-dehydro-7-deacetoxy-7-oxogedunin, and three methyl angolensate derivatives, 6-deacetoxydomesticulide D, 6-deacetoxydomesticulide D 21-methylether, and entangosin, together with known compounds, methyl angolensate, 6-acetoxymethyl angolensate and secomahoganin. Their structures were established by extensive NMR experiments in conjunction with mass spectrometry. Entangosin is a rare example of a limonoid derivative having a fully O-substituted furan moiety.