[Show abstract][Hide abstract] ABSTRACT: The stereochemistry of decarestrictine G was revised to be 5R,6R,9R from theoretical and synthetic studies. The presumable stereoisomer was estimated by comparison of the 1H NMR chemical shifts of the natural product with the calculated values based on density functional theory. With this finding, a synthetic study was performed, and the spectroscopic data for the synthetic (5R,6R,9R)-isomer was fully identical to those of the natural product. The synthesis of (5R,6R,9R)-(−)-decarestrictine G was achieved in 16.5% overall yield in six steps from methyl 3-oxohex-5-enoate via a ring-closing metathesis and a face-selective dihydroxylation of a ten-membered lactone system as the key steps.
[Show abstract][Hide abstract] ABSTRACT: Epicoccamides A and D were synthesized through a route that utilizes fragment coupling via olefin cross-metathesis as a key step. The right-hand segment of the epicoccamides was synthesized by a tandem O-acylation-migration reaction, and the left-hand segments were stereoselectively synthesized through a modified version of Crich's beta-selective mannosylation. The previously assigned absolute configuration of the epicoccamide D was confirmed, and that of epicoccamide A was assigned as (5S,2'S) based on the NMR and CD spectra. This Letter provides the first example of the total synthesis of epicoccamide A.
[Show abstract][Hide abstract] ABSTRACT: Communication among microorganisms is mediated by secretion and detection of microbial signaling molecules such as quorum-sensing pheromones and microbial hormones. The molecules elicit the regulation of important genes necessary for microbial survival and often play important roles in interspecies or even inter-kingdom communication. Recent progress in the study of the signaling molecules has enabled us to eavesdrop on microbial conversations to gain insight on their intercellular communication system. This review summarizes the recent advances in the chemistry and chemical biology of these important microbial signaling molecules: acyl-homoserine lactones (AHLs), AI-2, CAI-1 related alpha-hydroxy ketones (AHKs), ComX pheromones, diffusible signal factors (DSFs), diffusible extracellular factor (DF), and Phytophthora mating hormones. (C) 2014 Published by Elsevier Ltd.
[Show abstract][Hide abstract] ABSTRACT: The first enantioselective syntheses of ganomycin I, a meroterpenoid isolated from the Vietnamese mushroom Ganoderma colossum, and the related meroterpenoid fornicin A were accomplished. Our methodology for the total syntheses of these compounds featured the construction of the butenolide moiety by asymmetric dihydroxylation followed by Julia–Kocienski type olefin formation and ring‐closing metathesis reactions. The absolute configurations of the two natural products were determined by comparisons of specific rotation. A cell‐based assay of the synthetic compounds with transfected human embryonic kidney 293 tet‐off (E‐PR293) cells indicated that ganomycin I possesses cytotoxicity and fornicin A possesses weak anti‐HIV‐1 protease activity without cytotoxicity. The first enantioselective syntheses of meroterpenoids ganomycin I and fornicin A were achieved through the construction of their butenolide moiety by asymmetric dihydroxylation followed by Julia–Kocienski type olefination and ring‐closing metathesis reactions. Ganomycin I showed cytotoxicity, and fornicin A showed weak anti‐HIV‐1 protease activity without cytotoxicity.
European Journal of Organic Chemistry 02/2014; 2014(4). DOI:10.1002/ejoc.201301269 · 3.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor alpha (TNF-α), a central mediator of the inflammatory response, is released from basophilic cells and other cells in response to a variety of proinflammatory stimuli. Vialinin A is a potent inhibitor of TNF-α production and is released from RBL-2H3 cells. Ubiquitin-specific peptidase 5 (USP5), a deubiquitinating enzyme, was identified as a target molecule of vialinin A and its enzymatic activity was inhibited by vialinin A. Here we report production of TNF-α is decreased in USP5 siRNA-knockdown RBL-2H3 cells, compared with control cells. The finding of the present study strongly suggests that USP5 is one of the essential molecules for the production of TNF-α in RBL-2H3.
PLoS ONE 12/2013; 8(12):e80931. DOI:10.1371/journal.pone.0080931 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vialinin A, a small compound isolated from the Chinese mushroom Thelephora vialis, exhibits more effective anti-inflammatory activity than the widely used immunosuppressive drug tacrolimus (FK506). Here, we show that ubiquitin-specific peptidase 5/isopeptidase T (USP5/IsoT) is a target molecule of vialinin A, identified by using a beads-probe method. Vialinin A inhibited the peptidase activity of USP5/IsoT and also inhibited the enzymatic activities of USP4 among deubiquitinating enzymes tested. Although USPs are a member of thiol protease family, vialinin A exhibited no inhibitions for other thiol proteases, such as calpain and cathepsin.
[Show abstract][Hide abstract] ABSTRACT: The first total synthesis of virgineone aglycone has been achieved employing the tandem O-acylation–migration reaction and the olefin cross-metathesis as key steps for fragment couplings. The left-hand segment of virgineone was also synthesized. The absolute configuration of the reported virgineone aglycone was determined to be (2S,7RS,26S) based on NMR analyses and the specific rotation values of the synthetic compounds. The absolute configuration of the natural virgineone was presumed to be (2S,7S,26S) based on NMR analyses of the synthetic virgineone aglycone.
[Show abstract][Hide abstract] ABSTRACT: Synthesis of 2-homoprenyl-1-methyl-3-(5-methylfuran-2-yl)cyclopenta-2,4-dien-1-ol, the core framework of the proposed structure of the brown alga derived natural product sargafuran, was achieved in six steps from the commercially available 5-methylfurfural via the Piancatelli rearrangement of furylcarbinol. The concise synthetic route to the 1,2,3-trisubstituted cyclopentadienol is established. However, the 1H and 13C NMR spectral data of the synthetic analog of sargafuran suggest that the originally proposed structure of sargafuran must be incorrect. In addition, the structure of the natural sargafuran is also discussed.
[Show abstract][Hide abstract] ABSTRACT: A secondary metabolite of Streptomyces versipelis, versipelostatin(VST) A is a down-regulator of grp78 gene expression. This compound consists of a trisaccharide attached to a seventeen-membered macrocycle fused to spirotetronate and octalin units. Our interest in the its structural features and biological activity led us to pursue to its synthesis. In this study, we achieved the effective synthesis of the eastern unit of VST 4 via a coupling reaction of units 2 and 3. The spirotetronate unit 2 was synthesized from pulegone via tetronate formation and installation and quarterly center by Johnson-Claisen rearrangement. Syntheses of these units were accomplished in each ten or eleven steps, and provide good overall yields. Further synthetic studies toward the total synthesis of versipelostatin A are now in progress. O OH O OMe O Et O O NaPh CO 2 Me
The Twelfth International Conference of New Aspects of Organic Chemistry (IKCOC-12), Kyoto, JAPAN; 11/2012
[Show abstract][Hide abstract] ABSTRACT: Vialinin A is an extremely potent inhibitor of tumor necrosis factor (TNF)-α release from RBL-2H3 cells. The present study investigated in detail the inhibitory effects of vialinin A and its analog, 5',6'-dimethyl-1,1':4',1″-terphenyl-2',3',4,4″-tetraol (DMT), on TNF-α. Vialinin A and DMT inhibited the release of TNF-α from RBL-2H3 cells in a dose-dependent manner, but had no effect on β-hexosaminidase activity. Also, vialinins had little effect on TNF-α mRNA levels. Intriguingly, vialinins inhibited TNF-α production at low concentrations, but not shown a dose-dependency. The potent inhibitory activities of vialinins against TNF-α production and release suggest promising new candidate pathways for anti-inflammatory agents.
[Show abstract][Hide abstract] ABSTRACT: The synthesis of two potent osteoclast-forming suppressing agents isolated from the Chinese mushroom Agrocybe chaxingu, demethylincisterol A3 and chaxine A, was accomplished using ergocalciferol as the starting material. Our methodology for the synthesis of demethylincisterol A3 and chaxine A featured the construction of a butenolide moiety by the intramolecular Horner–Wadsworth–Emmons reaction under Masamune–Roush conditions. This is the first reported synthesis of chaxine A.
[Show abstract][Hide abstract] ABSTRACT: The synthesis of the spirotetronate unit of versipelostatin A, a down-regulator of molecular chaperone GRP78, was achieved in ten steps starting from pulegone, via the Johnson-Claisen rearrangement. A model study of the coupling reaction with the octalin unit was also performed.
[Show abstract][Hide abstract] ABSTRACT: The mating hormones α1 and α2 induce sexual reproduction of the phytopathogenic genus Phytophthora. To demonstrate the structural elements responsible to hormonal activity, 17 derivatives of α1 and α2 were synthesized and their hormonal activity (oospore-inducing activity) was evaluated. The terminal ester derivatives of α1 (diacetate and dibenzoate) retained the hormonal activity, whereas a dicarbamate derivative completely suppressed the activity. Even monocarbamates showed weak activities; among them the 1-O-carbamate was less active than 16-O-carbamate, suggesting that the 1-OH group is a little more important than 16-OH. Dihydro, dehydro, and demethyl derivatives exhibited the minimum level of activity. Surviving activity of 15-epi-α1 suggested a less importance of this stereochemistry. Contrary to α1, not only the terminal diacetate derivative but also monoacetates of α2 exhibited no or little activity. Among the monoacetates, 1-O-acetyl-α2 exhibited little yet relatively better activity than the others. No activity was observed for mono- and dicarbamoyl derivatives of α2. Dihydro α2 with the saturated double bond lost most of the activity. These findings suggest that both the mating hormones α1 and α2 require most of the functional (hydroxyl, keto, and olefinic) groups they possess in their natural form for inducing the sexual reproduction of Phytophthora.
[Show abstract][Hide abstract] ABSTRACT: Four stereoisomers of Phytophthora mating hormone α2 were synthesized using both enantiomers of citronellol as starting materials. The absolute configuration of the natural product was determined to be 7S,11R,15R by oospore-inducing assays of the synthetic isomers. A concise synthetic procedure of α1 was also established using a common synthetic intermediate of α2.