"Asymmetric Total Syntheses, Stereostructures, and Cytotoxicities of Marine Bromotriterpenoids Aplysiol B (Laurenmariannol) and Saiyacenol A" K. Nishikibe, K. Nishikawa, M. Kumagai, M. Doe, and Y. Morimoto Chem. Asian J. 17, e202101137 (2022) [ Open Access ].
Selected as Front Cover.
ABSTRACT: Total assignments of stereostructures of marine cytotoxic bromotriterpenoids, aplysiol B (laurenmariannol) and saiyacenol A, were accomplished through their asymmetric chemical syntheses to elucidate their ambiguous stereostructures and whether or not other members showing the opposite chirality for the ABC ring system exist. Moreover, their preliminary growth inhibitory activities against some tumor cells were also evaluated.
"Furanocembranoid from the Okinawan Soft Coral Sinularia sp." M. Nagasaka, K. Tani, K. Nishikawa, R. Kinjo, and T. Ishii Nat. Prod. Bioprospect. 12, Article number 7 (2022) [ Open Access ].
ABSTRACT: One new furanocembranoid diterpene, 11-hydroxy-Δ12(13)-pukalide (1), along with six known secondary metabolites, 11-acetoxy-Δ12(13)-pukalide (2), 13α-acetoxypukalide (3), pukalide (4), 3α-methoxyfuranocembranoid (5), Δ9(15)-africanene (6), and methyl (5′E)-5-(2′,6′-dimethylocta-5′,7′-dienyl)furan-3-carboxylate (7) were isolated from the Okinawan soft coral Sinularia sp. Their chemical structures were elucidated based on spectroscopic analysis (FTIR, NMR, and HRESIMS), and the relative stereochemistry of 1 was determined by NOESY experiments and acetylation, which yielded derivative 2. In addition, compounds 1 and 7 exhibited toxicity in the brine shrimp lethality test.
"Establishing a “Ring Size-Divergent” Synthetic Strategy: Synthesis, Structural Revision, and Absolute Configuration of Feroniellins" K. Nishikawa, T. Niwa, K. Nishikibe, M. Kumagai, and Y. Morimoto Chem. Eur. J. 27, 11045–11049 (2021).
ABSTRACT: A “ring-size-divergent” strategy enabled us to divergently synthesize the five-, six-, and seven-membered ether rings of feroniellin analogs from diepoxides under simple acidic or neutral conditions in only two steps from bergamottin. Additionally, the proposed structures of feroniellins A and B were revised, and the absolute configurations of all feroniellins were determined from their asymmetric synthesis.
"One‐Step Synthesis of the 1‐Azaspiro[5.5]undecane Skeleton Characteristic of Histrionicotoxin Alkaloids from Linear Substrates via Hg(OTf)2‐Catalyzed Cycloisomerization" K. Matsumura, K. Nishikawa, H. Yoshida, T. Niwa, Y. Fushii, M. Doe, and Y. Morimoto Chem. Asian J. 16, 1882–1886 (2021).
ABSTRACT: A one-step synthesis of the 1-azaspiro[5.5]undecane skeleton in histrionicotoxin alkaloids from a linear substrate was realized utilizing a Hg(OTf)2-catalyzed cycloisomerization reaction. Histrionicotoxin alkaloids as potential target drugs were successfully synthesized via our developed cyclization.
"Tetrodotoxin Framework Construction from Linear Substrates Utilizing a Hg(OTf)2-Catalyzed Cycloisomerization Reaction: Synthesis of the Unnatural Analogue 11-nor-6,7,8-Trideoxytetrodotoxin" K. Nishikawa, T. Noguchi, S. Kikuchi, T. Maruyama, Y. Araki, M. Yotsu-Yamashita, and Y. Morimoto Org. Lett. 23, 1703–1708 (2021).
ABSTRACT: 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.
"Natural Product Synthesis Strategy Based on the Concept of Directly Constructing the Ring Skeletons from Linear Substrates" K. Nishikawa, M. Kumagai, K. Matsumura, K. Nishikibe, and Y. Morimoto J. Synth. Org. Chem., Jpn. 79, 197-209 (2021).
ABSTRACT: Our concept of natural product synthesis is to directly construct the ring skeletons, frequently occurring in natural products with strong biological activities, from easily accessible linear substrates, and our group has established practical methods for synthesizing useful natural products along our synthetic strategy. First, we developed a cycloisomerization reaction to directly synthesize nitrogen-containing spirocycles from linear substrates, accompanied with construction of a stereogenic tetrasubstituted spiro-carbon. The reaction enabled us to achieve the efficient total synthesis of lepadiformines, revealing a phenomenon of their enantiodivergence. The synthesis of histrionicotoxins, frog poisons, was also accomplished through our original cyclization reaction. In addition, we found the critical switching of cyclization modes of polyepoxides in acidic aqueous media and neutral water, and the novel cascade cyclization was applied to the synthesis of natural products.
"4β-Hydroxywithanolide E and Withanolide E from Physalis peruviana L. Inhibit Adipocyte Differentiation of 3T3-L1 Cells through Modulation of Mitotic Clonal Expansion" M. Kumagai, I. Yoshida, T. Mishima, M. Ide, K. Fujita, M. Doe, K. Nishikawa, and Y. Morimoto J. Nat. Med. 75, 232–239 (2021).
ABSTRACT: 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. Activity-guided fractionation of the extract revealed 4β-hydroxywithanolide E (HWE) and withanolide E (WE) as the adipogenesis inhibitors. Both compounds suppressed mRNA expression of central adipogenic transcription factors, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer-binding protein α in the early stage of adipocyte differentiation. The inhibitory action of these two withanolides on adipogenesis was largely limited to this stage. The proliferation of preadipocytes was markedly suppressed by treatment with HWE and WE for 24 and 48 h in the differentiation medium, and cell-cycle arrest in the G0/G1 phase was observed. Therefore, our results suggested that withanolides from P. peruviana to be novel anti-adipogenic compounds that modulate mitotic clonal expansion.
”Use of Whole‐Body Cryosectioning and Desorption Electrospray Ionization Mass Spectrometry Imaging to Visualize Alkaloid Distribution in Poison Frogs" A. M. Jeckel, K. Matsumura, K. Nishikawa, Y. Morimoto, R. A. Saporito, T. Grant, and D. R. Ifa J. Mass Spectrom. 55, e4520 (2020).
ABSTRACT: 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. Our results show that whole-body cryosectioning coupled with histochemical staining and DESI-MSI is an effective technique to visualize alkaloid distribution and help elucidate the mechanisms involved in alkaloid sequestration in poison frogs.
"Fluorinated Kavalactone Inhibited RANKL-Induced Osteoclast Differentiation of RAW264 Cells" M. Kumagai, K. Nishikawa, T. Mishima, I. Yoshida, M. Ide, A. Watanabe, K. Fujita, and Y. Morimoto Biol. Pharm. Bull. 43, 898–903 (2020) [ Open Access ].
ABSTRACT: 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.
"Critical Switching of Cyclization Modes of Polyepoxides in Acidic Aqueous Media and Neutral Water: Synthesis and Revised Structure of a Nerolidol‐Type Sesquiterpenoid" K. Nishikawa, K. Morita, S. Hashimoto, A. Hoshino, T. Ikeuchi, M. Kumagai, and Y. Morimoto Angew. Chem. Int. Ed. 58, 10168–10172 (2019);
Angew. Chem. 131, 10274–10278 (2019).
Selected as Front Cover.
ABSTRACT: Biomimetic epoxide-opening cascades of polyepoxides enable the efficient and rapid construction of polyether frameworks. Herein, we show that the epoxide-opening cascade cyclization that affords tetrahydrofuran products in acidic aqueous media produces tetrahydropyran (THP) in neutral water. THP formation proceeded by simply heating polyepoxides in neutral water and followed a different cyclization mode from those observed so far. The novel cascade cyclization in H2O was applied to the synthesis of a new nerolidol-type sesquiterpenoid, resulting in revision of the proposed structure and determination of the absolute configuration.
“Formal Total Synthesis of Histrionicotoxin Alkaloids via Hg(OTf)2-catalyzed Cycloisomerization and SmI2-induced Ring Expansion” K. Matsumura, K. Nishikawa, H. Yoshida, M. Doe, and Y. Morimoto RSC Adv. 8, 11296-11303 (2018) [ Open Access ].
ABSTRACT: 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.
"Evaluation of Aculeatin and Toddaculin Isolated from Toddalia asiatica as Anti-inflammatory Agents in LPS-Stimulated RAW264 Macrophages" M. Kumagai, A. Watanabe, I. Yoshida, T. Mishima, M. Nakamura, K. Nishikawa, and Y. Morimoto Biol. Pharm. Bull. 41, 132-137 (2018) [ Open Access ].
ABSTRCT: 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.
"Total Syntheses of Lepadiformine Marine Alkaloids with Enantiodivergency, Utilizing Hg(OTf)₂-Catalyzed Cycloisomerization Reaction and Their Cytotoxic Activities" K. Nishikawa, K. Yamauchi, S. Kikuchi, S. Ezaki, T. Koyama, H. Nokubo, K. Matsumura, T. Kodama, M. Kumagai, and Y. Morimoto Chem. Eur. J. 23, 9535-9545 (2017).
Selected as Back Cover.
ABSTRACT: A phenomenon of enantiodivergence was found in lepadiformine alkaloids isolated from a single species marine tunicate Clavelina moluccensis through their syntheses. The enantioselective total syntheses have been achieved by a key mercury(II) triflate-catalyzed cycloisomerization reaction developed in our laboratory (see scheme), and cytotoxic activities of synthesized compounds were also evaluated.
"Synthesis of Novel 5,6-Dehydrokawain Analogs as Osteogenic Inducers and Their Action Mechanisms" M. Kumagaia, K. Nishikawa, T. Mishima, I. Yoshida, M. Ide, K. Koizumi, M. Nakamura, and Y. Morimoto Bioorg. Med. Chem. Lett. 27, 2401–2406 (2017).
ABSTRACT: 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. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity. Among the potential analogs we synthesized, (E)-6-(4-Ethylstyryl)-4-methoxy-2H-pyran-2-one (14) and (E)-6-(4-Butylstyryl)-4-methoxy-2H-pyran-2-one (21) both significantly up-regulated Runx2 and Osterix mRNA expression at 10 µM. These osteogenic activities could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast differentiation of RAW264 cells. These results indicated that novel 5,6-dehydrokawain analogs not only increase osteogenic activity but also inhibit osteoclast differentiation, and could be potential lead compounds for the development of anti-osteoporosis agents.
"Total Synthesis of the Cytotoxic Marine Triterpenoid Isodehydrothyrsiferol Reveals Partial Enantiodivergency in the Thyrsiferol Family of Natural Products" A. Hoshino, H. Nakai, M. Morino, K. Nishikawa, T. Kodama, K. Nishikibe, and Y. Morimoto Angew. Chem. Int. Ed. 56, 3064-3068 (2017);
Angew. Chem. 129, 3110–3114 (2017).
ABSTRACT: Enantioselective total synthesis of the cytotoxic marine triterpenoid isodehydrothyrsiferol revealed partial enantiodivergence in that the ABC ring system is enantiomeric to that of the other members of this natural product family. Furthermore, this unprecedented partial enantiodivergence is observed between dehydrothyrsiferol and isodehydrothyrsiferol, which originate from a single species, the red alga Laurencia viridis.
"Total Synthesis of Nitropyrrolins A, B, and D" H. Mitani, T. Matsuo, T. Kodama, K. Nishikawa, Y. Tachi, and Y. Morimoto Tetrahedron 72, 7179–7184 (2016).
ABSTRACT: The chemical synthetic method of cytotoxic nitropyrrolins A (1), B (2), and D (4), 2-nitropyrrole terpenoids rarely occurring in nature, has been developed for further biological studies. After the synthesis of nitropyrrolin B has first been achieved, nitropyrrolin B was transformed into nitropyrrolins A and D in two steps and one step, respectively. The regio- and stereoselective epoxide-cleavage reaction was highlighted in the direct conversion of nitropyrrolin B to D.
"5,6-Dehydrokawain from Alpinia zerumbet Promotes Osteoblastic MC3T3-E1 Cell Differentiation" M. Kumagai, T. Mishima, A. Watanabe, T. Harada, I. Yoshida, K. Fujita, M. Watai, S. Tawata, K. Nishikawa, and Y. Morimoto Biosci. Biotech. Biochem. 80, 1425-1432 (2016) [ Open Access ].
ABSTRACT: 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 aspromising 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. 5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells.
"Total Synthesis of (−)-Lepadiformine A Utilizing Hg(OTf)2-Catalyzed Cycloisomerization Reaction" K. Nishikawa, S. Kikuchi, S. Ezaki, T. Koyama, H. Nokubo, T. Kodama, Y. Tachi, and Y. Morimoto Org. Lett. 17, 5772-5775 (2015);
Highlighted in Synfacts 2, 116 (2016).
ABSTRACT: 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. Thus, we have accomplished the efficient total synthesis of (−)-lepadiformine A in 28% overall yield by featuring the novel Hg(OTf)2-catalyzed cycloisomerization.
"Total Synthesis and Complete Stereochemical Assignment of Heronapyrroles A and B" T. Matsuo, S. Hashimoto, K. Nishikawa, T. Kodama, S. Kikuchi, Y. Tachi, Y. Morimoto Tetrahedron Lett. 56, 5345-5348 (2015).
ABSTRCT: Heronapyrroles A and B with promising and selective antibacterial activity but no cytotoxicity against mammalian cell lines are among members of rare and unique 4-farnesylated-2-nitropyrrole natural products. The absolute configurations at C7 and C15 have been proposed to be 7S and 15R by the modified Mosher method. In this Letter, we have achieved the total synthesis of natural (+)-heronapyrroles A (1) and B (2) and report that the correct absolute configurations are 7R, 8S, and 15S as shown in the structural formulas 1 and 2.
"Biomimetic Total Synthesis of (-)-Neroplofurol and (+)-Ekeberin D4 Triggered by Hydrolysis of Terminal Epoxides" T. Kodama, S. Aoki, T. Matsuo, Y. Tachi, K. Nishikawa, and Y. Morimoto Chem. Lett. 43, 1662-1664 (2014).
ABSTRACT: To accumulate the chemical basis of epoxide-opening cascade biogenesis, chemical syntheses of sesqui- and triterpenoids were performed. The biomimetic total syntheses of (−)-neroplofurol (1) and (+)-ekeberin D4 (2) were accomplished by protic acid-catalyzed hydrolysis of the terminal epoxide from nerolidol diepoxide 3 and squalene tetraepoxide 4 through single and double 5-exo cyclizations in intermediates 5 and 6, respectively. This chemical reaction mimics the direct hydrolysis mechanism of epoxide hydrolases, enzymes that catalyze an epoxide-opening reaction to finally produce vicinal diols.
"Analysis of Enantiofacial Selective Epoxidation Catalyzed by Flavin-Containing Monooxygenase Lsd18 Involved in Ionophore Polyether Lasalocid Biosynthesis" G. Suzuki, A. Minami, M. Shimaya, T. Kodama, Y. Morimoto, H. Oguri, and H. Oikawa Chem. Lett. 43, 1779-1781 (2014).
ABSTRACT: Enzymatic epoxidation represents a key biosynthetic transformation in the construction of polyether skeletons. A single flavin-containing monooxygenase, Lsd18, is involved in ionophore polyether lasalocid biosynthesis and participates in the enantioselective epoxidations of the diene precursor. Biotransformation studies utilizing structurally simplified monoolefin analogs with different substitution patterns revealed important structural requirements for the enantiofacial selectivity of Lsd18-catalyzed epoxidations. These results enabled us to propose a substrate binding model of Lsd18, which was applied to the biosynthesis of other polyethers.
"A Convergent Total Synthesis of Antiplasmodial C2 Symmetric (+)-Ekeberin D4" T. Kodama, S. Aoki, S. Kikuchi, T. Matsuo, Y. Tachi, K. Nishikawa, and Y. Morimoto Tetrahedron Lett. 54, 5647-5649 (2013).
ABSTRACT: The first concise total synthesis of C2 symmetric (+)-ekeberin D4 (1) that exhibits antiplasmodial activity has been achieved in total nine steps and 27% yield from the known diol 4. The efficient synthetic method features the regio- and diastereoselective epoxidation of 4 and convergent coupling between half fragments 2 and 3 by taking into account the C2 symmetric property.
"Biomimetic Epoxide-Opening Cascades of Oxasqualenoids Triggered by Hydrolysis of the Terminal Epoxide" Y. Morimoto, E. Takeuchi, H. Kambara, T. Kodama, Y. Tachi, and K. Nishikawa Org. Lett. 15, 2966–2969 (2013).
ABSTRACT: 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.
"TIPSOTf-promoted Tandem Reaction through Rearrangement of Epoxides into Aldehydes with Selective Alkyl Migration Followed by Prins-Type Cyclization to Cyclopentanes" T. Kodama, S. Harada, T. Tanaka, Y. Tachi, and Y. Morimoto Synlett 3, 458-462 (2012)
ABSTRACT: The tandem reaction of trisubstituted epoxides to cyclopentanes promoted by TIPSOTf in nitromethane has been found. It consists of stereospecific rearrangement of epoxides into aldehydes accompanied with selective alkyl migration and subsequent Prins-type cyclization of the aldehydes generated to cyclopentanes.
"Total Synthesis of Marine Halogen-Containing Triterpene Polyethers Using Regioselective 5-exo and 6-endo Cyclizations and the Stereochemistry" Y. Morimoto J. Synth. Org. Chem., Jpn. 70, 154-165 (2012).
ABSTRACT: Aurilol (1), intricatetraol (3), and enshuol (5), marine halogen-containing members of a family of squalene-derived triterpene polyethers named oxasqualenoids, were isolated from the sea hare Dolabella auricularia, the red alga Laurencia inricata, and omaezakiana Masuda, respectively. Although their planar structures and partial configurations were elucidated by spectroscopic and chemical analyses, until now their entire configurations had not been determined. Many other types of oxasqualenoids have also been isolated from both marine and terrestrial organisms; however, it is often difficult to determine their stereostructures even by modern highly advanced spectroscopic methods, especially in the case of acyclic systems that include stereogenic quaternary carbon centers. Such systems expose the technical limitations of the current highly advanced NMR spectroscopic methods used for the structural elucidation of diverse and complex natural products. Herein, we report the total assignments of the previously incomplete stereostructures of 1, 3, and 5 to 2, 4, and 6, respectively, through the first asymmetric total syntheses featuring regioselective 5-exo and 6-endo cyclizations of bishomoepoxy alcohols.
“Diastereoselective Synthesis of the Indeno-tetrahydropyridine Core Bearing a Diaryl-substituted Stereogenic Quaternary Carbon Center of Haouamine B” T. Tanaka, H. Inui, H. Kida, T. Kodama, T. Okamoto, A. Takeshima, Y. Tachi and Y. Morimoto Chem. Commun. 47, 2949-2951 (2011).
ABSTRACT: The characteristic indeno-tetrahydropyridine core of cytotoxic haouamine B (2) was efficiently synthesized featuring the diastereoselective construction of a diaryl-substituted stereogenic quaternary center by an intramolecular Pd-catalyzed α-C-arylation and subsequent direct conversion of the vinylogous imide function into the C2–C25 double bond by TsNHNH2.
"Rings D-seco and B,D-seco Tetranortriterpenoids from Root Bark of Entandrophragma Angolense" T. K. Nsiama, H. Okamura, T. Hamada, Y. Morimoto, M. Doe, T. Iwagawa, and M. Nakatani Phytochemistry 72, 1854-1858 (2011).
“Cytotoxic Isomalabaricane Derivatives and a Monocyclic Triterpene Glycoside from the Sponge Rhabdastrella Globostellata” M. Hirashima, K.Tsuda, T. Hamada, H. Okamura, T. Furukawa, S. Akiyama, Y. Tajitsu, R. Ikeda, M. Komatsu, M. Doe, Y. Morimoto, M. Shiro, R. W. M. van Soest, K. Takemura, and T. Iwagawa J. Nat. Prod. 73, 1512-1518 (2010).
“Cytotoxic Biscembranes from the Soft Coral Saricophyton glaucum” T. Iwagawa, K. Hashimoto, Y. Yokogawa, H. Okamura, M. Nakatani, M. Doe, Y. Morimoto and K. Takemura J. Nat. Prod. 72, 946-949 (2009).
“Total Synthesis and Determination of the Absolute Configuration of (+)-Omaezakianol ” Y. Morimoto, T. Okita and H. Kambara Angew. Chem., Int. Ed. 48, 2538-2541 (2009).
Angew. Chem. 121, 2576-2579 (2009).
ABSTRACT: The first asymmetric total synthesis of the marine tetracyclic oxasqualenoid (+)-omaezakianol features a convergent olefin cross-metathesis between a monotetrahydrofuran fragment and a triepoxy alkene, and cascade oxacyclizations of a triepoxy alcohol to form the right-hand three ether rings. The total synthesis proved the absolute configuration of (+)-omaezakianol to be that shown.
“Squalene-Derived Triterpene Polyethers from the Red Alga Laurencia Omaezakiana” Y. Matsuo, M. Suzuki, M. Masuda, T. Iwai and Y. Morimoto Helv. Chim. Acta 91, 1261-1266 (2008).
ABSTRACT: In our continuing search on halogenated metabolites from species of the red algal genus Laurencia, a novel squalene-derived triterpene polyether, named omaezakianol (2), was isolated from Laurencia omaezakiana Masuda along with 15,16-anhydrothyrsiferol (3). Their structures were determined by spectral and chemical methods.
“Limonoids from the Stem Bark of Cedrela Odorata” N. T. Kipassa, T. Iwagawa, H. Okamura, M. Doe, Y. Morimoto, and M. Nakatani Photochemistry 69, 1782-1787 (2008).
“The Role of Chemical Synthesis in Structure Elucidation of Oxasqualenoids” Y. Morimoto Org. Biomol. Chem. 6, 1709-1719 (2008).
ABSTRACT: Recently, highly oxidized and structurally diverse triterpene polyethers, which are thought to be biogenetically squalene-derived natural products (oxasqualenoids), have been isolated from both marine and terrestrial organisms. However, it is often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic quaternary carbon centers. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, we report total assignments of the previously incomplete stereostructures of an epoxy tri-THF diol, intricatetraol and enshuol, members of the oxasqualenoids, through the first asymmetric total syntheses of the natural products, the configurations of which are difficult to determine by other means. Since this article is basically written as a communication without detailed experimental procedures and spectroscopic data, original papers with full data should follow.
“Three Mexicanolides from the Root Bark of Entandrophragma Angolense” T. N. Kipassa, H. Okamura, M. Doe, Y. Morimoto, T. Iwagawa, and M. Nakatani Heterocycles 75, 157-164 (2008).
“Assignment of the Absolute Configuration of the Marine Pentacyclic Polyether (+)-Enshuol by Total Synthesis” Y. Morimoto, H. Yata, and Y. Nishikawa Angew. Chem., Int. Ed. 46, 6481-6484 (2007);
Angew. Chem. 119, 6601-6604 (2007).
ABSTRACT: The complete stereostructure of the marine pentacyclic triterpene polyether (+)-enshuol is shown. Asymmetric total synthesis confirmed the configuration predicted on the basis of NMR spectroscopic data of the previously synthesized natural products aurilol and glabrescol, substructures of which are present in enshuol, and disproved an earlier prediction based on biogenetic considerations.
“Total Synthesis and Determination of the Absolute Configuration of (+)-Intricatetraol” Y. Morimoto, T. Okita, M. Takaishi, and T. Tanaka Angew. Chem., Int. Ed. 46, 1132-1135 (2007);
Angew. Chem. 119, 1150-1153 (2007).
ABSTRACT: The total synthesis of the marine triterpene polyether (+)-intricatetraol (1) has revealed its absolute configuration, which could not be determined even by spectroscopic methods. The approach features the enantioselective construction of the unique vicinal bromochloro functionality and an efficient olefin-metathesis strategy that takes the C2 symmetry of the target into consideration.
“Two-directional Synthesis and Stereochemical Assignment toward a C-2 Symmetric Oxasqualenoid (+)-Intricatetraol ” Y. Morimoto, M. Takaishi, N. Adachi, T. Okita, and H.Yata Org. Biomol. Chem. 4, 3220-3222 (2006).
ABSTRACT: The asymmetric synthesis of tetraol (+)-3, a degradation product derived from a C2 symmetric oxasqualenoid intricatetraol 1, has been achieved through the two-directional synthesis starting from diol 7, realizing the further additional assignment of the incomplete stereostructure of 1, the stereochemistry of which is difficult to determine otherwise.
“Reagent-Controlled Swiching of 5-exo to 6-endo Cyclizations in Epoxide Openings” Y. Morimoto, Y. Nishikawa, C. Ueba, and T. Tanaka Angew. Chem., Int. Ed. 45, 810-812 (2006);
Angew. Chem. 118, 824-826 (2006).
ABSTRACT: The switching of the usual 5-exo cyclizations of epoxide substrates to the 6-endo mode, which goes against Baldwin's rule, is demonstrated by treating bishomoepoxy alcohols with triisopropylsilyl triflate (TIPSOTf) in nitromethane (see scheme). This method is different to those previously reported in which elaborate modifications of the epoxide substrate are required to attain 6-endo cyclization.
“Structure, Biological Activities, and Total Syntheses of 13-Hydroxy- and 13-Acetoxy-14-nordehydrocacalohastine, Novel Modified Furanoeremophilane-type Sesquiterpenes from Trichilia Cuneata” M. Doe, T. Shibue, H. Haraguchi and Y. Morimoto Org. Lett. 7, 1765-1768 (2005).
ABSTRACT: 13-Hydroxy-14-nordehydrocacalohastine (2) and 13-acetoxy-14-nordehydrocacalohastine (3), two novel modified furanoeremophilane-type sesquiterpenes isolated from Trichilia cuneata, showed inhibitory activities for membrane lipid peroxidation in mitochondria and microsomes. The first, highly convergent total syntheses of new compounds 2 and 3 have also been achieved via a palladium-mediated three-component coupling reaction between 2-iodotoluene (7), 1-penten-4-yn-3-ol (8), and diethyl ethoxymethylenemalonate (9).
“Total Synthesis and Complete Assignment of the Stereostructure of a Cytotoxic Bromotriterpene Polyether (+)-Aurilol” Y. Morimoto, Y. Nishikawa and M. Takaishi J. Am. Chem. Soc. 127, 5806-5807 (2005).
“Structure, Synthesis, and Biological Activity of 14-Methoxy-1,2-dehydrocacalol Methyl Ether, a New Modified Furanoeremophilane Type Sesquiterpene from trichilia cuneata” M. Doe, Y. Hirai, T. Kinoshita, K. Shibata, H. Haraguchi and Y. Morimoto Chem. Lett. 33, 714-715 (2004).
“Total Synthesis of Five Cacalol Families at Different Oxidation Stages, Modified Furanoeremophilane Sesquiterpenes from Cacalia and Senecio Species” Y. Hirai, M. Doe, T. Kinoshita and Y. Morimoto Chem. Lett. 33, 136-137 (2004).
“Total Synthesis and Asssignment of the Double-Bond Position and Absolute Configuration of (-)-Pyrinodemin A” Y. Morimoto, T. Iwai, S. Kitao, T. Okita and T. Shoji Org. Lett. 5, 2611-2614 (2003).
“Stereospecific and Biomimetic Synthesis of CS and C2 Symmetric 2,5-Disubstituted Tetahydrofuran Rings as Central Building Blocks of Biogenetically Intriguing Oxasqualenoids” Y. Morimoto, T. Iwai, Y. Nishikawa and T. Kinoshita Tetrahedron: Asymmetry 13, 2641-2647 (2002).
“Complete Assignment of the Stereostructure of a New Squalene-Derived Epoxy Tri-THF Diol from Spathelia glabrescens by Total Synthesis” Y. Morimoto, M. Takaishi, T. Iwai, T. Kinoshita, H. Jacobs Tetrahedron Lett. 43, 5849-5852 (2002).
“Total Synthesis and Determination of the Stereochemistry of 2-Amino-3-cyclopropylbutanoic Acid, a Novel Plant Growth Regulator Isolated from the Mushroom Amanita Castanopsidis Hongo” Y. Morimoto, M. Takaishi, T. Kinoshita, K. Sakaguchi and K. Shibata Chem. Commun. 42-43 (2002).
"Synthesis and Absolute Configuration of Lactone II Isolated from Streptomyces sp. Go 40/10" T. Ueki, Y. Morimoto and T. Kinoshita Chem. Commun. 1820-1821 (2001).
"Total Synthesis and Determination of the Absolute Configuration of (−)-Iongilene Peroxide" Y. Morimoto, T. Iwai and T. KinoshitaTetrahedron Lett. 42, 6307-6309 (2001).
"Stereocontrolled Total Synthesis of the Stemona Alkaloid (−)-Stenine" Y. Morimoto, M. Iwahashi, T. Kinoshita and K. Nishida Chem. Eur. J. 7, 4107–4116 (2001).
“Total Synthesis of (+)-Eurylene and (+)-14-Deacetyl Eurylene” Y. Morimoto, K. Muragaki, T. Iwai, Y. Morishita and T. Kinoshita Angew. Chem., Int. Ed. 39, 4082-4084 (2000).
“Revised Structure of Squalene-Derived Penta THF Polyether, Glabrescol, through Its Enantioselective Total Synthesis: Biogenetically Intriguing CS vs C2 Symmetric Relationships” Y. Morimoto, T. Iwai and T. Kinoshita J. Am. Chem. Soc. 122, 7124-7125 (2000).
"Can α-Sultone Exist as a Chemical Species ? First Experimental Implication for Intermediacy of α-Sultone” Y. Morimoto, H. Kurihara and T. Kinoshita Chem. Commun. 189-190 (2000).
“Effective Combination of Two-Directional Synthesis and Rhenium(VII) Chemistry: Total Synthesis of meso Polyether Teurilene” Y. Morimoto, T. Iwai and T. Kinoshita J. Am. Chem. Soc. 121, 6792-6797 (1999).
“Total Syntheses of Macrocyclic Marine Alkaloids, Haliclamines A and B: A Convenient and Expeditious Assembly of 3-Substituted Pyridine Derivatives with Different Alkyl Chains to the Bispyridinium Macrocycle” Y. Morimoto, C. Yokoe, H. Kurihara and T. Kinoshita Tetrahedron 54, 12197-12214 (1998).
“Highly Diastereoselective Cyclizations of Bishomoallylic Tertiary Alcohols Promoted by Rhenium(VII) Oxide. Critical Steric versus Chelation Effects in Alkoxyrhenium Intermediates” Y. Morimoto and T. Iwai J. Am. Chem. Soc. 120, 1633-1634 (1998).
"Synthesis and Asolute Configuration of (+)-Hyperolactone B" T. Ueki, D. Ichinari, K. Yoshihara, Y. Morimoto and T. Kinoshita Tetrahedron Lett. 39, 667-668 (1998).
"Diastereoselective Two-directional Synthesis and Cation Transport Ability of the Central Tristetrahydrofuranyl Unit of Meso Polyether Glabrescol as Naturally Occurring Podand" Y. Morimoto, T. Iwai, T. Yoshimura, T. Kinoshita Bioorg. Med. Chem. Lett. 8, 2005-2010 (1998).
“Unexpected Stability of δ-Lactones with Axial Substituents rather than Equatorial Ones. Conformational Evaluation by Molecular Mechanics and Molecular Orbital Calculations” Y. Morimoto and H. Shirahama Tetrahedron 53, 2013-2024 (1997).
"Stereocontrolled Synthesis of C10-C22 Fragment of the Iimmunosuppressant FK 506. An Occurrence of Complementary Stereoselectivity in the C15 Ketone Reduction" Y. Morimoto, A. Mikami, S. Kuwabe and H. Shirahama Tetrahedron: Asymmetry 7, 3371-3390 (1996).
“Synthetic Studies on Virantmycin. 2. Total Synthesis of Unnatural (+)-Virantmycin and Determination of Its Absolute Stereochemistry” Y. Morimoto and H. Shirahama Tetrahedron 52, 10631-10652 (1996).
"Synthetic Studies on Virantmycin. 1. Total Synthesis of (±)-Virantmycin and Determination of Its Relative Stereochemistry" Y. Morimoto, F. Matsuda and H. Shirahama Tetrahedron 52, 10609-10630 (1996).
“Studies on the Asymmetric Synthesis of Stemona Alkaloids: Total Synthesis of (-)-Stenine” Y. Morimoto, M. Iwahashi, K. Nishida, Y. Hayashi and H. Shirahama Angew. Chem., Int. Ed. 35, 904-906 (1996).
"水銀トリフラート触媒による新奇環化異性化反応を鍵工程としたアザ三環性アルカロイド(－)-レパジホルミンAの全合成" 第94化学会春季年会 ○菊池正峰、江崎伸之介、小山智之、野久保春華、児玉猛、西川慶祐、舘祥光、森本善樹 (口頭、3月、名古屋)
"デヒドロチルシフェロールとその類縁体の全合成研究" 第94化学会春季年会 ○中井遥、星野晃大、森野光耶子、神原瞳、滝直人、西川慶祐、舘祥光、森本善樹 (口頭、3月、名古屋)
"三脚型ヘテロトリアリール配位子を用いた錯体形成過程におけるコア構造の効果" 第94化学会春季年会 ○角高海理、西川慶祐、森本善樹、舘祥光 (口頭、3月、名古屋)
"ジプロリン骨格を有する新規鉄錯体の合成と機能" 第94化学会春季年会 ○山口颯人、西川慶祐、森本善樹、舘祥光 (口頭、3月、名古屋)
"三脚型トリヘテロアリール配位子を用いた配位高分子形成過程の解明" 第94化学会春季年会 ○田村哲平、西川慶祐、森本善樹、舘祥光 (口頭、3月、名古屋)
"L-prolineから誘導される不斉配位子を導入した鉄錯体の電気化学的な酸化反応の検討" 第94化学会春季年会 ○溝口晃平、西川慶祐、森本善樹、舘祥光 (口頭、3月、名古屋)
"テトロドトキシンの合成研究” 第34回有機化学若手セミナー ○菊池正峰、吉山春香、西川慶祐、舘祥光、森本善樹 (ポスター、8月、大阪)
”海洋産細胞毒性ポリエーテルiubol推定構造式の不斉全合成” 第34回有機合成若手セミナー ○滝直人、中井遥、星野晃大、森野光耶子、西川慶祐、舘祥光、森本善樹 (ポスター、8月、大阪)
”水銀(Ⅱ)トリフラート触媒を用いた新奇環化異性化反応によるテトロドトキシンモデル化合物の合成研究” 第34回有機合成若手セミナー ◯丸山高弘、菊池正峰、小山智之、西川慶祐、舘祥光、森本善樹 (ポスター、8月、大阪)
”水銀(Ⅱ)トリフラート触媒を用いた新奇環化異性化反応によるテトロドトキシンモデル化合物の合成研究” 第44回複素環化学討論会 ◯丸山高弘、菊池正峰、小山智之、西川慶祐、舘祥光、森本善樹 (ポスター、9月、札幌)
”海洋産細胞毒性ポリエーテルiubol推定構造式の不斉全合成” 第44回複素環化学討論会 ○滝直人、中井遥、星野晃大、森野光耶子、西川慶祐、舘祥光、森本善樹 (口頭、9月、札幌)
"α-リポ酸光学異性体/γ-シクロデキストリン包接複合体の溶液中での挙動" 第31回シクロデキストリンシンポジウム ○土江松美、西川慶祐、舘祥光、森本善樹 (ポスター、9月、島根)
"非対称型配位子を用いた多核鉄錯体の構造及びその反応性" 錯体化学会第64回討論会 ○中尾拓人、舘祥光、森本善樹、西川慶祐 (ポスター、9月、東京)
"三脚型トリへテロアリール配位子を用いた銅錯体形成過程の構造解明” 錯体化学会第64回討論会 ○角高海理、田村哲平、西川慶祐、森本善樹、舘祥光 (口頭、9月、東京)
"4‒ファルネシル-2-ニトロピロール天然物の全合成” 第56回天然有機化合物討論会 松尾知樹、三谷光、○児玉猛、西川慶祐、舘祥光、森本善樹 (ポスター、10月、高知)
"水銀トリフラート触媒による新奇環化異性化反応を鍵工程とした(－)-レパジホルミンAの全合成" 第106回有機合成シンポジウム(秋) ◯菊池正峰、江崎伸之介、小山智之、野久保春華、児玉猛、西川慶祐、舘祥光、森本善樹 (口頭及びポスター、11月、東京)
"非対称ペンタピリジン配位子を導入した新規鉄錯体の合成" 第93化学会春季年会 ○中尾拓人、森本善樹、舘祥光 (口頭、3月、草津)
"α位置換金属フタロシアニンの合成" 第93化学会春季年会 ○青柳貞利、森本善樹、舘祥光 (口頭、3月、草津)
"イソデヒドロチルシフェロールの収束的な全合成" 第93化学会春季年会 ○中井遥、星野晃大、森野光耶子、神原瞳、児玉猛、菊池正峰、舘祥光、森本善樹 (口頭、3月、草津)
"仮想生合成経路に基づく(+)-エケベリンD4の全合成研究" 第93化学会春季年会 ○児玉猛、青木慎悟、松尾知樹、舘祥光、森本善樹 (口頭、3月、草津)
"ヘロナピロールA 及びB の全合成" 第93化学会春季年会 ○松尾知樹、三谷光、児玉猛、舘祥光、森本善樹 (口頭、3月、草津)
"ニトロピロリン類の合成研究" 第93化学会春季年会 ○三谷光、松尾知樹、児玉猛、舘祥光、森本善樹 (口頭、3月、草津)
"金属触媒を用いた新奇環化異性化反応によるテトロドトキシンの合成研究" 第93化学会春季年会 ○菊池正峰、吉山春香、小山智之、舘祥光、森本善樹 (口頭、3月、草津)
"神経毒性テトロドトキシンの合成研究" 第93化学会春季年会 ○吉山春香、小山智之、菊池正峰、舘祥光、森本善樹 (口頭、3月、草津)
"(－)-レパジホルミン A の合成研究" 第93化学会春季年会 ○江崎伸之介、小山智之、舘祥光、森本善樹 (口頭、3月、草津)
"ヘロナピ ロール類A及びBの全合成と全立体構造の決定" 第33回有機化学若手セミナー ○松尾知樹、三谷光、児玉猛、西川慶祐、舘祥光、森本善樹 (ポスター、8月、神戸)
"海洋産含臭素化合物isodehydrothyrsiferolの全合成と全立体構造の決定" 第33回有機合成若手セミナー ○中井遥、星野晃大、森野光耶子、神原瞳、児玉猛、菊池正峰、西川慶祐、舘祥光、森本善樹 (ポスター、8月、神戸)
"水銀トリフラート触媒による新奇環化異性化反応を鍵工程とした(－)-レパジホルミンAの全合成" 第33回有機合成若手セミナー ○菊池正峰、江崎伸之介、 小山智之、野久保春華、児玉猛、西川慶祐、舘祥光、森本善樹 (ポスター、8月、神戸) 優秀研究発表賞
"イノラートを用いた環化反応を鍵反応としたstemonamineの全合成" 第33回有機合成若手セミナー ○西川慶祐、池永大、松本健司、新藤充 (ポスター、8月、神戸)
"α-リポ酸シクロデキストリン包接複合体の溶液中での挙動" 第30回シクロデキストリンシンポジウム ○土江松美、河井昌裕、西川慶祐、舘 祥光、森本善樹 (ポスター、9月、熊本)
"水銀トリフラート触媒による新奇環化異性化反応を鍵工程としたアザ三環性アルカロイド(－)-レパジホルミンAの全合成" 第55回天然有機化合物討論会 ○菊池正峰、江崎伸之介、小山智之、野久保春華、児玉猛、西川慶祐、舘祥光、森本善樹 (口頭、9月、京都)
"L-prolineから誘導される新規不斉合成触媒の合成と酸化反応活性の検討" 錯体化学会第63回討論会 〇溝口晃平、西川慶祐、森本善樹、舘祥光 (口頭、11月、沖縄)
"非対称ペンタピリジン配位子を用いた鉄錯体の合成と構造及びその反応性" 錯体化学会第63回討論会 〇中尾拓人、西川慶祐、森本善樹、舘祥光 (口頭、11月、沖縄)
"不均一な配位場を有する三脚型配位子を用いた配位高分子合成と発光特性" 錯体化学会第63回討論会 〇田村哲平、西川慶祐、森本善樹、舘祥光 (ポスター、11月、沖縄)
"ヘロナピ ロール類A及びBの全合成と全立体構造の決定" 化学人材育成プログラム学生・企業交流会 ○松尾知樹、三谷光、児玉猛、西川慶祐、舘祥光、森本善樹 (ポスター、12月、大阪)