The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Makoto Sasaki - One of the best experts on this subject based on the ideXlab platform.
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total synthesis and complete structural assignment of gambieric acid a a large Polycyclic Ether marine natural product
ChemInform, 2014Co-Authors: Makoto Sasaki, Haruhiko FuwaAbstract:More than thirty years after the discovery of Polycyclic Ether marine natural products, they continue to receive intense attention from the chemical, biological, and pharmacological communities because of their potent biological activities and highly complex molecular architectures. Gambieric acids are intriguing Polycyclic Ethers that exhibit potent antifungal activity with minimal toxicity against mammals. Despite the recent advances in the synthesis of this class of natural products, gambieric acids remain unconquered due to their daunting structural complexity, which poses a formidable synthetic challenge to organic chemists. This paper reviews our long-term studies on the total synthesis, complete configurational reassignment, and structure-activity relationships of gambieric acid A over the last decade.
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recent applications of the suzuki miyaura cross coupling to complex Polycyclic Ether synthesis
ChemInform, 2012Co-Authors: Haruhiko Fuwa, Makoto Ebine, Makoto SasakiAbstract:The ladder-shaped Polycyclic Ether marine natural products present formidable and challenging synthetic targets due to their structural complexity, and exceptionally potent biological activities. Over the past decade, however, the limited availability of these substances from natural sources has precluded detailed biological studies. There has been an urgent need for means to supply useful quantities of these natural products and their analogues by total synthesis. We have developed a highly convergent strategy for the rapid and efficient assembly of Polycyclic Ether arrays, which relies on the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of cyclic enol triflates or phosphates. The utility of this strategy has been demonstrated by its application to the convergent total synthesis of the Polycyclic Ether class of natural products.
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synthetic studies on gambieric acids potent antifungal Polycyclic Ether natural products reassignment of the absolute configuration of the nonacyclic polyEther core by nmr analysis of model compounds
Journal of Organic Chemistry, 2009Co-Authors: Haruhiko Fuwa, T Goto, Kazuya Ishigai, Akihiro Suzuki, Makoto SasakiAbstract:A highly stereocontrolled, convergent synthesis of the A/B-ring fragment of gambieric acids (GAs) has been developed on the basis of (i) a Suzuki−Miyaura coupling of the C1−C6 alkylborate and the C7−C17 vinyl iodide and (ii) a diastereoselective haloEtherification for the construction of the A-ring tetrahydrofuran as key steps. Inspection of the 1H and 13C NMR chemical shifts of the synthesized A/B-ring model compounds led to a stereochemical reassignment of the absolute configuration of the Polycyclic Ether core of GAs. This structure revision was further supported by a synthesis of the A/BC-ring model compound of gambieric acid B and a comparison of its 1H and 13C NMR data with those of the natural product.
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stereocontrolled synthesis of the a b ring fragment of gambieric acid b reassignment of the absolute configuration of the Polycyclic Ether region
Organic Letters, 2008Co-Authors: Haruhiko Fuwa, T Goto, Makoto SasakiAbstract:Stereocontrolled synthesis of the A/B-ring fragment of the originally assigned structure of gambieric acid B and its possible diastereomers has been accomplished. Detailed comparison of their 1H and 13C NMR data with those of the corresponding moiety of the natural product culminated in a stereochemical reassignment of the absolute configuration of the Polycyclic Ether region of gambieric acid B.
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Convergent strategies for the total synthesis of Polycyclic Ether marine metabolites.
Natural product reports, 2008Co-Authors: Makoto Sasaki, Haruhiko FuwaAbstract:Marine Polycyclic Ether natural products continue to fascinate chemists and biologists due to their exceptionally large and complex molecular architectures and potent and diverse biological activities. Tremendous progress has been made over the past decade toward the total synthesis of marine Polycyclic Ether natural products. In this area, a convergent strategy for assembling small fragments into an entire molecule always plays a key role in successful total synthesis. This review describes our efforts to develop convergent strategies for the synthesis of Polycyclic Ethers and their application to the total synthesis of gambierol, gymnocin-A, and brevenal, and to the partial synthesis of the central part of ciguatoxins and the nonacyclic polyEther skeleton of gambieric acids.
Haruhiko Fuwa - One of the best experts on this subject based on the ideXlab platform.
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Synthesis-Driven Stereochemical Assignment of Marine Polycyclic Ether Natural Products
MDPI AG, 2021Co-Authors: Haruhiko FuwaAbstract:Marine Polycyclic Ether natural products have gained significant interest from the chemical community due to their impressively huge molecular architecture and diverse biological functions. The structure assignment of this class of extraordinarily complex natural products has mainly relied on NMR spectroscopic analysis. However, NMR spectroscopic analysis has its own limitations, including configurational assignment of stereogenic centers within conformationally flexible systems. Chemical shift deviation analysis of synthetic model compounds is a reliable means to assign the relative configuration of “difficult” stereogenic centers. The complete configurational assignment must be ultimately established through total synthesis. The aim of this review is to summarize the indispensable role of organic synthesis in stereochemical assignment of marine Polycyclic Ethers.
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total synthesis and complete structural assignment of gambieric acid a a large Polycyclic Ether marine natural product
ChemInform, 2014Co-Authors: Makoto Sasaki, Haruhiko FuwaAbstract:More than thirty years after the discovery of Polycyclic Ether marine natural products, they continue to receive intense attention from the chemical, biological, and pharmacological communities because of their potent biological activities and highly complex molecular architectures. Gambieric acids are intriguing Polycyclic Ethers that exhibit potent antifungal activity with minimal toxicity against mammals. Despite the recent advances in the synthesis of this class of natural products, gambieric acids remain unconquered due to their daunting structural complexity, which poses a formidable synthetic challenge to organic chemists. This paper reviews our long-term studies on the total synthesis, complete configurational reassignment, and structure-activity relationships of gambieric acid A over the last decade.
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recent applications of the suzuki miyaura cross coupling to complex Polycyclic Ether synthesis
ChemInform, 2012Co-Authors: Haruhiko Fuwa, Makoto Ebine, Makoto SasakiAbstract:The ladder-shaped Polycyclic Ether marine natural products present formidable and challenging synthetic targets due to their structural complexity, and exceptionally potent biological activities. Over the past decade, however, the limited availability of these substances from natural sources has precluded detailed biological studies. There has been an urgent need for means to supply useful quantities of these natural products and their analogues by total synthesis. We have developed a highly convergent strategy for the rapid and efficient assembly of Polycyclic Ether arrays, which relies on the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of cyclic enol triflates or phosphates. The utility of this strategy has been demonstrated by its application to the convergent total synthesis of the Polycyclic Ether class of natural products.
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synthetic studies on gambieric acids potent antifungal Polycyclic Ether natural products reassignment of the absolute configuration of the nonacyclic polyEther core by nmr analysis of model compounds
Journal of Organic Chemistry, 2009Co-Authors: Haruhiko Fuwa, T Goto, Kazuya Ishigai, Akihiro Suzuki, Makoto SasakiAbstract:A highly stereocontrolled, convergent synthesis of the A/B-ring fragment of gambieric acids (GAs) has been developed on the basis of (i) a Suzuki−Miyaura coupling of the C1−C6 alkylborate and the C7−C17 vinyl iodide and (ii) a diastereoselective haloEtherification for the construction of the A-ring tetrahydrofuran as key steps. Inspection of the 1H and 13C NMR chemical shifts of the synthesized A/B-ring model compounds led to a stereochemical reassignment of the absolute configuration of the Polycyclic Ether core of GAs. This structure revision was further supported by a synthesis of the A/BC-ring model compound of gambieric acid B and a comparison of its 1H and 13C NMR data with those of the natural product.
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stereocontrolled synthesis of the a b ring fragment of gambieric acid b reassignment of the absolute configuration of the Polycyclic Ether region
Organic Letters, 2008Co-Authors: Haruhiko Fuwa, T Goto, Makoto SasakiAbstract:Stereocontrolled synthesis of the A/B-ring fragment of the originally assigned structure of gambieric acid B and its possible diastereomers has been accomplished. Detailed comparison of their 1H and 13C NMR data with those of the corresponding moiety of the natural product culminated in a stereochemical reassignment of the absolute configuration of the Polycyclic Ether region of gambieric acid B.
Masahiro Hirama - One of the best experts on this subject based on the ideXlab platform.
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structural and energetic hot spots for the interaction between a ladder like Polycyclic Ether and the anti ciguatoxin antibody 10c9fab
Molecular BioSystems, 2011Co-Authors: Masahiro Hirama, Masayuki Inoue, Yoshikazu Tanaka, Takeshi Tsumuraya, Ikuo Fujii, Kouhei TsumotoAbstract:The mechanism by which anti-ciguatoxin antibody 10C9Fab recognizes a fragment of ciguatoxin CTX3C (CTX3C-ABCDE) was investigated by mutational analysis based on structural data. 10C9Fab has an extraordinarily large and deep antigen-binding pocket at the center of its variable region. We mutated several residues located at the antigen-binding pocket to Ala, and kinetic analysis of the interactions between the mutant proteins and the antigen fragment was performed. The results indicate that some residues associated with the rigid antigen-binding pocket are structural hot-spots and that L-N94 is an energetic hot-spot for association of the antibody with the antigen fragment CTX3C-ABCDE, suggesting the importance of structural complementarity and energetic hot-spot interactions for specific recognition of Polycyclic Ethers.
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how protein recognizes ladder like Polycyclic Ethers interactions between ciguatoxin ctx3c fragments and its specific antibody 10c9
Journal of Biological Chemistry, 2008Co-Authors: Yoshikazu Tanaka, Masahiro Hirama, Masayuki Inoue, Takeshi Tsumuraya, Ikuo Fujii, Kouhei TsumotoAbstract:Ciguatoxins are a family of marine toxins composed of transfused Polycyclic Ethers. It has not yet been clarified at the atomic level on the pathogenic mechanism of these toxins or the interaction between a Polycyclic Ether compounds and a protein. Using the crystal structures of anti-ciguatoxin antibody 10C9 Fab in ligand-free form and in complexes with ABCD-ring (CTX3C-ABCD) and ABCDE-ring (CTX3C-ABCDE) fragments of the antigen CTX3C at resolutions of 2.6, 2.4, and 2.3A, respectively, we elucidated the mechanism of the interaction between the Polycyclic Ethers and the antibody. 10C9 Fab has an extraordinarily large and deep binding pocket at the center of the variable region, where CTX3C-ABCD or CTX3C-ABCDE binds longitudinally in the pocket via hydrogen bonds and van der Waals interactions. Upon antigen-antibody complexation, 10C9 Fab adjusts to the antigen fragments by means of rotational motion in the variable region. In addition, the antigen fragment lacking the E-ring induces a large motion in the constant region. Consequently, the thermostability of 10C9 Fab is enhanced by 10 °C upon complexation with CTX3C-ABCDE but not with CTX3C-ABCD. The crystal structures presented in this study also show that 10C9 Fab recoginition of CTX3C antigens requires molecular rearrangements over the entire antibody structure. These results further expand the fundamental understanding of the mechanism by which ladder-like Polycyclic Ethers are recognized and may be useful for the design of novel therapeutic agents by antibodies, marine toxins, or new diagnostic reagents for the detection and targeting of members of the Polycyclic Ether family.
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convergent synthesis of the abcde ring fragment of the caribbean ciguatoxin c ctx 1
ChemInform, 2007Co-Authors: Masayuki Inoue, Fumihito Saito, Masafumi Iwatsu, Yuuki Ishihara, Masahiro HiramaAbstract:Abstract Ciguatoxin C-CTX-1 was isolated as a principal causative toxin of ciguatera seafood poisoning in the Caribbean Sea, and is structurally classified as a ladder-shaped Polycyclic Ether. In this Letter, we report the convergent synthesis of the pentacyclic left half of C-CTX-1, based on a newly developed acyl radical strategy.
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synthesis of the lmn ring fragment of the caribbean ciguatoxin c ctx 1
ChemInform, 2007Co-Authors: Keita Yoshikawa, Masayuki Inoue, Masahiro HiramaAbstract:Abstract Ciguatoxin C-CTX-1 was isolated as a principal causative toxin of ciguatera seafood poisoning in the Caribbean Sea, and is structurally classified as a ladder-shaped Polycyclic Ether. In this Letter, we report the synthesis of the tricyclic LMN-ring system of C-CTX-1. SmI 2 -mediated reductive cyclization efficiently constructed the seven-membered M-ring with the axially oriented 1,3-dimethyl structure.
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effect of ciguatoxin 3c on voltage gated na and k currents in mouse taste cells
Chemical Senses, 2006Co-Authors: Valeria Ghiaroni, Haruhiko Fuwa, Makoto Sasaki, Masahiro Hirama, Masayuki Inoue, Takeshi Yasumoto, Keisuke Miyazaki, Gian Paolo Rossini, Giuseppe Scalera, Albertino BigianiAbstract:The marine dinoflagellate Gambierdiscus toxicus produces highly lipophilic, Polycyclic Ether toxins that cause a seafood poisoning called ciguatera. Ciguatoxins (CTXs) and gambierol represent the two major causative agents of ciguatera intoxication, which include taste alterations (dysgeusiae). However, information on the mode of action of ciguatera toxins in taste cells is scarce. Here, we have studied the effect of synthetic CTX3C (a CTX congener) on mouse taste cells. By using the patch-clamp technique to monitor membrane ion currents, we found that CTX3C markedly affected the operation of voltage-gated Na + channels but was ineffective on voltage-gated K + channels. This result was the exact opposite of what we obtained earlier with gambierol, which inhibits K + channels but not Na + channels. Thus, CTXs and gambierol affect with high potency the operation of separate classes of voltage-gated ion channels in taste cells. Our data suggest that taste disturbances reported in ciguatera poisoning might be due to the ability of ciguatera toxins to interfere with ion channels in taste buds.
Masayuki Satake - One of the best experts on this subject based on the ideXlab platform.
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interaction analysis of a ladder shaped Polycyclic Ether and model transmembrane peptides in lipid bilayers by using forster resonance energy transfer and polarized attenuated total reflection infrared spectroscopy
Bioorganic & Medicinal Chemistry, 2014Co-Authors: Kazuya Yamada, Masayuki Satake, Haruki Kuriyama, Toshiaki Hara, Michio Murata, Raku Irie, Yanit Harntaweesup, Seketsu Fukuzawa, Kazuo TachibanaAbstract:Ladder-shaped Polycyclic Ethers (LSPs) are predicted to interact with membrane proteins; however, the underlying mechanism has not been satisfactorily elucidated. It has been hypothesized that LSPs possess non-specific affinity to α-helical segments of transmembrane proteins. To verify this hypothesis, we constructed a model LSP interaction system in a lipid bilayer. We prepared 5 types of α-helical peptides and reconstituted them in liposomes. The reconstitution and orientation of these peptides in the liposomes were examined using polarized attenuated total reflection infrared (ATR-IR) spectroscopy and gel filtration. The results revealed that 4 peptides were retained in liposomes, and 3 of them formed stable transmembrane structures. The interaction between the LSP and the peptides was investigated using Forster resonance energy transfer (FRET). In the lipid bilayer, the LSP strongly recognized the peptides that possessed aligned hydrogen donating groups with leucine caps. We propose that this leucine-capped 16-amino acid sequence is a potential LPS binding motif.
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brevisulcenal f a Polycyclic Ether toxin associated with massive fish kills in new zealand
Journal of the American Chemical Society, 2012Co-Authors: Yuka Hamamoto, Kazuo Tachibana, Patrick T Holland, Feng Shi, Veronica Beuzenberg, Yoshiyuki Itoh, Masayuki SatakeAbstract:A novel marine toxin, brevisulcenal-F (KBT-F, from karenia brevisulcata toxin) was isolated from the dinoflagellate Karenia brevisulcata. A red tide of K. brevisulcata in Wellington Harbour, New Zealand, in 1998 was extremely toxic to fish and marine invertebrates and also caused respiratory distress in harbor bystanders. An extract of K. brevisulcata showed potent mouse lethality and cytotoxicity, and laboratory cultures of K. brevisulcata produced a range of novel lipid-soluble toxins. A lipid soluble toxin, KBT-F, was isolated from bulk cultures by using various column chromatographies. Chemical investigations showed that KBT-F has the molecular formula C107H160O38 and a complex Polycyclic Ether nature. NMR and MS/MS analyses revealed the complete structure for KBT-F, which is characterized by a ladder-frame polyEther scaffold, a 2-methylbut-2-enal terminus, and an unusual substituted dihydrofuran at the other terminus. The main section of the molecule has 17 contiguous 6- and 7-membered Ether rings. T...
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total synthesis of brevisin a concise synthesis of a new marine Polycyclic Ether
ChemInform, 2011Co-Authors: Takefumi Kuranaga, Jeffrey L. C. Wright, Daniel G. Baden, Masayuki Satake, Naohito Ohtani, Ryosuke Tsutsumi, Kazuo TachibanaAbstract:The first total synthesis of (I) succeeds in 29 steps from commercially available deoxy-D-ribose.
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total synthesis of brevisin a concise synthesis of a new marine Polycyclic Ether
Organic Letters, 2011Co-Authors: Takefumi Kuranaga, Jeffrey L. C. Wright, Daniel G. Baden, Masayuki Satake, Naohito Ohtani, Ryosuke Tsutsumi, Kazuo TachibanaAbstract:The first and highly efficient total synthesis of (−)-brevisin has been achieved. The title compound was synthesized in only 29 steps (longest linear sequence) from commercially available starting materials. The synthesis provided over 70 mg of a marine Polycyclic Ether compound.
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Brevisin: an aberrant Polycyclic Ether structure from the dinoflagellate Karenia brevis and its implications for polyEther assembly.
The Journal of organic chemistry, 2009Co-Authors: Masayuki Satake, Andrea J. Bourdelais, Henry M. Jacocks, Daniel G. Baden, Ryan M. Van Wagoner, Anna Campbell, Jeffrey L. C. WrightAbstract:Brevisin is an unprecedented Polycyclic Ether isolated from the dinoflagellate Karenia brevis, an organism well-known to produce complex Polycyclic Ethers. The structure of brevisin was determined by detailed analyses of MS and 2D NMR spectra and is remarkable in that it consists of two separate fused polyEther ring assemblies linked by a methylene group. One of the Polycyclic moieties contains a conjugated aldehyde side chain similar to that recently observed in other K. brevis metabolites, though the “interrupted” polyEther structure of brevisin is novel and provides further insight into the biogenesis of such fused-ring polyEther systems. On the basis of the unusual structure of brevisin, principles underlying the initiation of polyEther assemblies are proposed. Brevisin was found to inhibit the binding of [3H]-PbTx-3 to its binding site on the voltage-sensitive sodium channels in rat brain synaptosomes.
Tadashi Nakata - One of the best experts on this subject based on the ideXlab platform.
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synthetic studies on maitotoxin 3 stereoselective synthesis of the bcde ring system
Organic Letters, 2008Co-Authors: Masanori Satoh, Hiroyuki Koshino, Tadashi NakataAbstract:The stereoselective synthesis of the BCDE-ring system of maitotoxin has been accomplished through a two-directional strategy for the construction of Polycyclic Ether. The key reactions involve SmI2-induced double cyclization of a β-alkoxyacrylate and a double dihydroxylation for construction of the B- and E-rings.
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stereoselective synthesis of the ghi ring of maitotoxin a marine Polycyclic Ether
Heterocycles, 2007Co-Authors: Masanori Satoh, Masaki Mori, Tadashi NakataAbstract:The GHI-ring of maitotoxin, a marine Polycyclic Ether, was stereoselectively synthesized by way of SmI 2 -induced reductive cyclization of β-alkoxyacrylate and aldehyde.
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synthesis of cyclic Ether via intramolecular acyloin condensation
Heterocycles, 2006Co-Authors: Tatsuo Saito, Atsushi Kimishima, Tadashi NakataAbstract:Polycyclic Ether was synthesized via intramolecular acyloin condensation and Lewis acid-promoted silane reduction.
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stereoselective convergent synthesis of a trans fused Polycyclic Ether ring system including a 4 hydroxy 5 methyl tetrahydropyran ring
Organic Letters, 2002Co-Authors: Keisuke Suzuki, Tadashi NakataAbstract:Stereoselective convergent synthesis of a trans-fused 6-6-6-6-membered tetracyclic Ether ring system including 4α- or 4β-hydroxy-5-methyl-tetrahydropyran was achieved. The key reactions involve the acetylide-aldehyde coupling of two tetrahydropyrans, intramolecular hetero-Michael cyclization of enone, stereoselective reduction of enone, hydroboration, intramolecular acetalization, and stereoselective reduction of the acetal with Et3SiH−TMSOTf.
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efficient strategy for the iterative synthesis of trans fused Polycyclic Ether via smi2 induced reductive intramolecular cyclization
Tetrahedron, 2002Co-Authors: Nobuyuki Hori, Hiroko Matsukura, Goh Matsuo, Tadashi NakataAbstract:Abstract A highly efficient strategy for the iterative synthesis of a trans -fused Polycyclic Ether ring system has been developed. The new iterative method involves SmI 2 -induced reductive intramolecular cyclization of an aldehyde and a β-alkoxy acrylate as the key step, producing a 2,3- trans -tetrahydropyran or oxepane ring. The syntheses of trans -fused 6,6,6-tricyclic, 6,7,6-tricyclic, and 6,7,7,6-tetracyclic Ethers were effectively achieved based on the newly developed method.