研究者データベース

梅澤 大樹(ウメザワ タイキ)
地球環境科学研究院 物質機能科学部門 生体物質科学分野
准教授

基本情報

所属

  • 地球環境科学研究院 物質機能科学部門 生体物質科学分野

職名

  • 准教授

学位

  • 博士(理学)(大阪市立大学)

ホームページURL

科研費研究者番号

  • 20503618

ORCID ID

J-Global ID

研究キーワード

  • 含塩素化合物   全合成   クロロスルフォリピッド   有機合成化学   ブロモペルオキシダーゼ   ウラソゾ   紅藻   ハロゲン   付着生物   フジツボ   Laurencin   付着阻害   Omaezallene   ローレンシン   天然物合成   有機合成   Natural Product Synthesis   Organic Synthesis   

研究分野

  • ナノテク・材料 / 生物分子化学
  • ライフサイエンス / 水圏生命科学
  • ナノテク・材料 / 生物分子化学

職歴

  • 2013年 北海道大学 地球環境科学研究科(研究院) 准教授
  • 2008年 - 北海道大学大学院地球環境科学研究院 助教

学歴

  •         - 2006年   大阪市立大学   理学研究科   物質分子系専攻
  •         - 2006年   大阪市立大学
  •         - 2001年   大阪市立大学   理学部   物質科学科
  •         - 2001年   大阪市立大学

所属学協会

  • 日本農芸化学会   日本付着生物学会   有機合成化学協会   日本化学会   

研究活動情報

論文

  • Chin-Soon Phan, Jakia Jerin Mehjabin, Andrea Roxanne J. Anas, Masahiro Hayasaka, Reiko Onoki, Juting Wang, Taiki Umezawa, Kenji Washio, Masaaki Morikawa, Tatsufumi Okino
    Journal of Natural Products 2022年08月10日
  • Taiki Umezawa, Misaki Hara, Nana Kinoshita-Terauchi, Fuyuhiko Matsuda
    Organics 3 3 187 - 195 2022年07月 
    The total synthesis of multifidene, a sex pheromone found in brown algae, is described. The synthesis features the highly enantioselective and diastereoselective addition reaction of an aldehyde to a nitroolefin in the presence of a Hayashi–Jørgensen catalyst and a Nef reaction initiated by visible light irradiation. These key reactions enabled the 11-step synthesis from commercially available compounds. The synthetic pheromones are examined with gametes.
  • Loida O Casalme, Keisuke Katayama, Yoshiki Hayakawa, Kensuke Nakamura, Arisa Yamauchi, Yasuyuki Nogata, Erina Yoshimura, Fuyuhiko Matsuda, Taiki Umezawa
    Marine drugs 20 2 2022年02月04日 
    Some derivatives of dolastatin 16, a depsipeptide natural product first obtained from the sea hare Dolabella auricularia, were synthesized through second-generation synthesis of two unusual amino acids, dolaphenvaline and dolamethylleuine. The second-generation synthesis enabled derivatizations such as functionalization of the aromatic ring in dolaphenvaline. The derivatives of fragments and whole structures were evaluated for antifouling activity against the cypris larvae of Amphibalanus amphitrite. Small fragments inhibited the settlement of the cypris larvae at potent to moderate concentrations (EC50 = 0.60-4.62 μg/mL), although dolastatin 16 with a substituent on the aromatic ring (24) was much less potent than dolastatin 16.
  • Nurcahyo Iman Prakoso, Fuyuhiko Matsuda, Taiki Umezawa
    Organic & biomolecular chemistry 19 36 7822 - 7826 2021年09月22日 
    An efficient synthesis of α,β-dichlorinated ketones from α,β-dichlorinated Weinreb amides is described. Quenching with nonaqueous HCl avoided side reactions associated with typical work-up procedures. The amide reacted with various nucleophiles to give the corresponding ketones in high yields. A novel reactivity of the Weinreb amide is also discussed.
  • Taiki Umezawa, Nakaba Mizutani, Koichi Matsuo, Yuugo Tokunaga, Fuyuhiko Matsuda, Tatsuo Nehira
    Molecules (Basel, Switzerland) 26 5 2021年02月27日 
    A new application of vacuum-ultraviolet circular dichroism (VUVCD), which enables the measurement of CD spectra in the vacuum-ultraviolet region (140-200 nm), for the assignment of the absolute configurations of bromoallenes is described. Bromoallene moieties are found in natural products obtained from many marine organisms. To date, the absolute configuration of bromoallenes has been assigned almost exclusively with Lowe's rule, which is based on specific rotation. However, exceptions to Lowe's rule have been reported arising from the presence of other substituents with large specific rotations. For the unambiguous assignment of the absolute configuration of the bromoallene moiety with its characteristic absorption wavelength at 180-190 nm due to the π-π* transition, VUVCD was applied to four pairs of bromoallene diastereomers prepared by modifying the synthetic scheme of omaezallene. The VUVCD spectra clearly showed positive or negative Cotton effects around 180-190 nm according to the configuration of the bromoallene employed, revealing the potential of VUVCD for determining absolute stereochemistry.
  • Jakia Jerin Mehjabin, Liang Wei, Julie G. Petitbois, Taiki Umezawa, Fuyuhiko Matsuda, Charles S. Vairappan, Masaaki Morikawa, Tatsufumi Okino
    Journal of Natural Products 83 6 1925 - 1930 2020年05月20日 [査読有り][通常論文]
     
    Chemical investigation of the organic extract from Moorea bouillonii, collected in Sabah, Malaysia, led to the isolation of three new chlorinated fatty acid amides, columbamides F (1), G (2), and H (3). The planar structures of 1-3 were established by a combination of mass spectrometric and NMR spectroscopic analyses. The absolute configuration of 1 was determined by Marfey's analysis of its hydrolysate and chiral-phase HPLC analysis after conversion and esterification with Ohrui's acid, (1S,2S)-2-(anthracene-2,3-dicarboximido)cyclohexanecarboxylic acid. Compound 1 showed biosurfactant activity by an oil displacement assay. Related known fatty acid amides columbamide D and serinolamide C exhibited biosurfactant activity with critical micelle concentrations of about 0.34 and 0.78 mM, respectively.
  • Wontae Kim, Loida O. Casalme, Taiki Umezawa, Fuyuhiko Matsuda, Ryoichi Otomo, Yuichi Kamiya
    Chemistry Letters 49 1 71 - 74 2020年01月05日
  • Taiki Umezawa, Masayuki Shibata, Ryutaro Tamagawa, Fuyuhiko Matsuda
    Organic letters 21 19 7731 - 7735 2019年10月04日 
    We investigated the diastereoselectivity of ring openings for chloro vinyl epoxides with various chlorination reagents. In the chlorinolysis reactions using vinyl epoxides having an allyl alcohol, inversion:retention ratios varied depending on the chloride sources. In limited cases, the increase in retention ratio was consistent with the intervention of chloronium ions. In contrast, all vinyl epoxides bearing an α,β-unsaturated ester gave only the inversion products. These results suggest the electron-withdrawing property suppressed the chloronium ions.
  • Kinoshita-Terauchi, Nana, Shiba, Kogiku, Umezawa, Taiki, Matsuda, Fuyuhiko, Motomura, Taizo, Inaba, Kazuo
    Journal of photochemistry and photobiology. B, Biology 192 113 - 123 ELSEVIER SCIENCE SA 2019年03月 [査読有り][通常論文]
     
    Male gametes of the brown alga Mutimo cylindricus show positive phototaxis soon after spawning in seawater but gradually change the sign of phototaxis with time. This conversion appears to need the decrease of intracellular Ca concentration. In this study, we revealed that the conversion of male gamete phototactic sign, positive to negative, was accelerated by mixing with female gametes. The supernatant after the centrifugation of female gamete suspension showed the same activity to change the phototactic sign, suggesting that a factor released from female gametes was responsible for the reaction. A known brown algal sex pheromone, ectocarpene, induced chemotaxis of male gametes of M. cylindricus. The addition of this compound induced the change of phototactic sign, clearly indicating that a sex pheromone is essential for the reversal. An inhibitor of phosphodiesterase, theophylline, inhibited the chemotaxis and phototactic sign reversion by a factor released from female gametes and ectocarpene. Measurements of cyclic nucleotides showed that the increase in intracellular concentration of cAMP, not cGMP, was parallel to the change of phototactic sign. The inhibition of phototactic s
  • Kinoshita-Terauchi Nana, Shiba Kogiku, Umezawa Taiki, Matsuda Fuyuhiko, Motomura Taizo, Inaba Kazuo
    JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 192 113 - 123 2019年03月 [査読有り][通常論文]
     
    Male gametes of the brown alga Mutimo cylindricus show positive phototaxis soon after spawning in seawater but gradually change the sign of phototaxis with time. This conversion appears to need the decrease of intracellular Ca2+ concentration. In this study, we revealed that the conversion of male gamete phototactic sign, positive to negative, was accelerated by mixing with female gametes. The supernatant after the centrifugation of female gamete suspension showed the same activity to change the phototactic sign, suggesting that a factor released from female gametes was responsible for the reaction. A known brown algal sex pheromone, ectocarpene, induced chemotaxis of male gametes of M. cylindricus. The addition of this compound induced the change of phototactic sign, clearly indicating that a sex pheromone is essential for the reversal. An inhibitor of phosphodiesterase, theophylline, inhibited the chemotaxis and phototactic sign reversion by a factor released from female gametes and ectocarpene. Measurements of cyclic nucleotides showed that the increase in intracellular concentration of cAMP, not cGMP, was parallel to the change of phototactic sign. The inhibition of phototactic sign by theophylline was not observed in low Ca2+ sea water. These results suggest that a signaling pathway mediated by cAMP and Ca2+ concentrations drives the interconversion between two important behaviors of male gametes, phototaxis and chemotaxis.
  • Taiki Umezawa, Nurcahyo Iman Prakoso, Miho Kannaka, Yasuyuki Nogata, Erina Yoshimura, Tatsufumi Okino, Fuyuhiko Matsuda
    Chemistry & biodiversity 16 1 e1800451  2019年01月 [査読有り][通常論文]
     
    Omaezallene derivatives (nor-bromoallene, nor-bromodiene, and bromoenynes) were successfully synthesized. Their antifouling activity and toxicity to the cypris larvae of the barnacle Amphibalanus amphitrite and ecotoxicity to the marine crustacean Tigriopus japonicus were studied. It was revealed that the two side chains of omaezallene were essential to its antifouling activity because the activities of nor-bromoallene and nor-bromodiene were significantly diminished. The bromoenyne was found to exhibit potent antifouling activities comparable to omaezallene with low toxicity and ecotoxicity. Preparation of bromoenyne framework is much easier than that of bromodiene moiety in omaezallene. Based on the antifouling activities of the bromoenynes, the synthesis of fluorescent probes and evaluation of their biological activities were also carried out.
  • Taiki Umezawa
    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 76 5 426 - 429 2018年 [査読有り][通常論文]
     
    Details for the total synthesis of omaezallene, an antifouling natural product obtained from Laurencia sp, are described. Toward the total synthesis, tasks to be solved by total synthesis were determinations of relative configurations between bromoallene and THF ring, and the absolute configuration at C9 position. The use of an aldehyde, prepared from D-glucose in 5 steps, as a starting material was envisioned to accomplish these tasks. Although reactions for construction of the bromoallene and the THF ring were successful, extensive efforts to install the bromodiene unit were essential to overcome unexpected results.
  • Momochika Kumagai, Keisuke Nishikawa, Hiroshi Matsuura, Taiki Umezawa, Fuyuhiko Matsuda, Tatsufumi Okino
    Molecules 23 5 2018年 [査読有り][通常論文]
     
    An investigation of anti-oxidative compounds from the brown alga Dictyopteris undulata has led to the isolation and identification of isozonarol, isozonarone, chromazonarol, zonaroic acid and isozonaroic acid. Their structures were identified by comparison of MS and NMR spectra. Full NMR assignment and absolute configuration of isozonaroic acid are described. Isozonarol showed the most potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity among the compounds isolated.
  • Julie G. Petitbois, Loida O. Casalme, Julius Adam V. Lopez, Walied M. Alarif, Ahmed Abdel-Lateff, Sultan S. Al-Lihaibi, Erina Yoshimura, Yasuyuki Nogata, Taiki Umezawa, Fuyuhiko Matsuda, Tatsufumi Okino
    JOURNAL OF NATURAL PRODUCTS 80 10 2708 - 2715 2017年10月 [査読有り][通常論文]
     
    NMR-and MS-guided fractionation of an extract of an Okeania sp. marine cyanobacterium, collected from the Red Sea, led to the isolation of four new metabolites, including serinolamides C (1) and D (2) and lyngbyabellins O (3) and P (4), together with the three known substances lyngbyabellins F (5) and G (6) and dolastatin 16 (7). The planar structures of the new compounds were determined using NMR and MS analyses. The absolute configurations of 1 and 2 were determined by Marfey's analysis of their hydrolysates. The absolute configuration of 3 was ascertained by chiral-phase chromatography of degradation products, while that of 4 was determined by comparison to 3 and 5. The cytotoxic and antifouling activities of these compounds were evaluated using MCF7 breast cancer cells and Amphibalanus amphitrite larvae, respectively. Compounds 3, 4, and 7 exhibited strong antifouling activity, and 3 and 7 were not cytotoxic. A structure-activity relationship was observed for the cytotoxicity of the lyngbyabellins with the presence of a side chain (4 is more active than 3) leading to greater activity. For the antifouling activity, the acyclic form without a side chain (3) was the most active.
  • Suzuki J, Miyano N, Yashiro S, Umezawa T, Matsuda F
    Organic & biomolecular chemistry 15 31 6557 - 6566 2017年08月 [査読有り][通常論文]
     
    A 3,4-disubstituted pyrrolidine ring was effectively cyclized through SmI2-mediated reductive coupling between allyl chloride and an alpha,beta-unsaturated ester, although little has been reported about SmI2-promoted C-C bond formation of an allyl chloride with an alpha,beta-unsaturated ester. Selection of either the 3,4-cis- or 3,4-trans-selective cyclization can be accomplished simply by changing the additives from NiI2 to HMPA during reductive cyclization conducted in H2O-THF. Total synthesis of (-)-kainic acid and (+)-allo-kainic acid, which are pyrrolidine alkaloids used in neuroscience and neuropharmacology as useful molecular probes, was successfully achieved by using the stereo-complementary ring closure reactions promoted by SmI2 for the construction of the 2,3,4-trisubsituted pyrrolidine scaffold of kainoids.
  • Julius Adam V. Lopez, Julie G. Petitbois, Charles S. Vairappan, Taiki Umezawa, Fuyuhiko Matsuda, Tatsufumi Okino
    ORGANIC LETTERS 19 16 4231 - 4234 2017年08月 [査読有り][通常論文]
     
    Two new chlorinated fatty acid amides, columbamides D (1) and E (2), along with apratoxins A and C and wewakazole, were isolated from the organic extract of a Moorea bouillonii sample from Sabah, Malaysia. Structure elucidation was accomplished by a combination of MS and NMR analyses. The total synthesis of all four stereoisomers of 1 was completed, and the absolute configuration was determined by chiral-phase HPLC and Marfey's analysis.
  • Taiki Umezawa, Yuki Hasegawa, Ira S. Novita, Junya Suzuki, Tatsuya Morozumi, Yasuyuki Nogata, Erina Yoshimura, Fuyuhiko Matsuda
    MARINE DRUGS 15 7 2017年07月 [査読有り][通常論文]
     
    Biofouling, an undesirable accumulation of organisms on sea-immersed structures such as ship hulls and fishing nets, is a serious economic issue whose effects include oil wastage and clogged nets. Organotin compounds were utilized since the 1960s as an antifouling material; however, the use of such compounds was later banned by the International Maritime Organization (IMO) due to their high toxicity toward marine organisms, resulting in masculinization and imposex. Since the ban, there have been extensive efforts to develop environmentally benign antifoulants. Natural antifouling products obtained from marine creatures have been the subject of considerable attention due to their potent antifouling activity and low toxicity. These antifouling compounds often contain isocyano groups, which are well known to have natural antifouling properties. On the basis of our previous total synthesis of natural isocyanoterpenoids, we envisaged the installation of an isocyano functional group onto glucosamine to produce an environmentally friendly antifouling material. This paper describes an effective synthetic method for various glucosamine-based isocyanides and evaluation of their antifouling activity and toxicity against cypris larvae of the barnacle Amphibalanus amphitrite. Glucosamine isocyanides with an ether functionality at the anomeric position exhibited potent antifouling activity, with EC50 values below 1 mu g/mL, without detectable toxicity even at a high concentration of 10 mu g/mL. Two isocyanides had EC50 values of 0.23 and 0.25 mu g/mL, comparable to that of CuSO4, which is used as a fouling inhibitor (EC50 = 0.27 mu g/mL).
  • Loida O. Casalme, Arisa Yamauchi, Akinori Sato, Julie G. Petitbois, Yasuyuki Nogata, Erina Yoshimura, Tatsufumi Okino, Taiki Umezawa, Fuyuhiko Matsuda
    ORGANIC & BIOMOLECULAR CHEMISTRY 15 5 1140 - 1150 2017年02月 [査読有り][通常論文]
     
    The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite.
  • Kinoshita, N., Shiba, K., Inaba, K., Umezawa, T., Motomura, T.
    Phycologia 2017年
  • Taiki Umezawa, Keisuke Nishikawa, Tatsufumi Okino, Fuyuhiko Matsuda
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 74 7 689 - 699 2016年07月 [査読有り][通常論文]
     
    Biofouling is adverse growth of marine organisms on manmade submersible structures such as ships' hulls and cause significant economic and environmental problems. As a fouling inhibitor, tributyltin (TBT) has been widely used for controlling the sessile organisms since the early 1960s. Unfortunately, serious pollution of the marine environment due to the deleterious effect of TBT prompted the International Maritime Organization (IMO) to call in 2008 for a ban on the use of tributyltin (TBT) on ships. Since marine invertebrates prevent settlement of other benthic marine organisms through the use of natural substances with antifouling properties without causing serious environmental problems, natural antifouling products with good antifouling properties but without biocidal properties have attracted considerable attention. Among these, 10-isocyano-4-cadinene and omaezallene show promise as lead compounds for the development of new environmentally friendly antifouling agents due to its potent antifouling activity against the cypris larvae of the barnacle Amphibalanus amphitrite and low toxicity. 10-Isocyano-4-cadinene, an isocyanosesquiterpene, was isolated from nudibranchs of the family Phyllidiidae. On the other hand, omaezallene is a bromoallene-containing C-15-acetogenin isolated from the red alga Laurencia sp. Herein, we wish to describe our research on the isolations, structure elucidations, total syntheses, and evaluation of the antifouling activities of the natural products and their derivatives. The absolute configurations of the natural products were unambiguously established through our asymmetric total syntheses.
  • Taiki Umezawa, Akinori Sato, Yasuto Ameda, Loida O. Casalme, Fuyuhiko Matsuda
    TETRAHEDRON LETTERS 56 1 168 - 171 2015年01月 [査読有り][通常論文]
     
    A convenient and scalable synthesis of two unusual amino acid units found in dolastatin 16, dolaphenvaline, and dolamethylleuine, is described. Dolastatin 16, which was first isolated from the sea hare Dolabella auricularia by Pettit, exhibits not only strong inhibition of growth for a variety of human cancer cell lines but also potent antifouling activity against the larvae of the barnacle Balanus amphitrite. The key element of the synthesis is an organocatalytic Mannich reaction to construct two contiguous stereocenters in the amino acid units with almost complete enantio- and diastereoselectivity. (C) 2014 Elsevier Ltd. All rights reserved.
  • Kensuke Kaneko, Kenji Washio, Taiki Umezawa, Fuyuhiko Matsuda, Masaaki Morikawa, Tatsufumi Okino
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 78 8 1310 - 1319 2014年08月 [査読有り][通常論文]
     
    The marine red alga genus Laurencia is one of the richest producers of unique brominated compounds in the marine environment. The cDNAs for two Laurencia nipponica vanadium-dependent bromoperoxidases (LnVBPO1 and LnVBPO2) were cloned and expressed in Escherichia coli. Enzyme assays of recombinant LnVBPO1 and LnVBPO2 using monochlorodimedone revealed that they were thermolabile but their K-m values for Br- were significantly lower than other red algal VBPOs. The bromination reaction was also assessed using laurediol, the predicted natural precursor of the brominated ether laurencin. Laurediol, protected by trimethylsilyl at the enyne, was converted to deacetyllaurencin by the LnVBPOs, which was confirmed by tandem mass spectrometry. Native LnVBPO partially purified from algal bodies was active, suggesting that LnVBPO is functional in vivo. These results contributed to our knowledge of the biosynthesis of Laurencia brominated metabolites.
  • Taiki Umezawa, Fuyuhiko Matsuda
    TETRAHEDRON LETTERS 55 19 3003 - 3012 2014年05月 [査読有り][通常論文]
     
    Chlorosulfolipids (CSLs) are an intriguing family of natural products featuring highly chlorinated linear hydrocarbon skeletons. Although CSLs were first isolated in 1962, chemical synthesis of CSLs was hampered because relevant methods for stereoselective construction of the polychlorinated motifs of CSLs were scarce. Since Carreira's first total synthesis of the CSL mytilipin A in 2009, several groups, including our own, have reported total syntheses of CSLs. As a result of these total syntheses, important progress has been made in the development of reliable synthetic methods for stereoselective polychlorination. In this digest, we summarize the total syntheses of CSLs by focusing on synthetic methods for stereoselective polychlorination of the organic frameworks of CSLs. (c) 2014 Published by Elsevier Ltd.
  • Taiki Umezawa, Yuko Oguri, Hiroshi Matsuura, Shohei Yamazaki, Masahiro Suzuki, Erina Yoshimura, Takeshi Furuta, Yasuyuki Nogata, Yukihiko Serisawa, Kazuyo Matsuyama-Serisawa, Tsuyoshi Abe, Fuyuhiko Matsuda, Minoru Suzuki, Tatsufumi Okino
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 53 15 3909 - 3912 2014年04月 [査読有り][通常論文]
     
    Natural antifouling products have been the subject of considerable attention. We screened marine algae for antifouling activity and discovered omaezallenes, the new bromoallene-containing natural products isolated from the red alga Laurenciasp. Described is the isolation, structure elucidation, and total syntheses of omaezallenes. The relative and absolute configurations of natural omaezallenes were unambiguously established through total synthesis. The antifouling activities and ecotoxicity of omaezallenes were also evaluated.
  • Keisuke Nishikawa, Taiki Umezawa, Mary J. Garson, Fuyuhiko Matsuda
    JOURNAL OF NATURAL PRODUCTS 75 12 2232 - 2235 2012年12月 [査読有り][通常論文]
     
    The marine sponge metabolite 10-isothiocyanato4-cadinene (1) was first isolated by Garson et al. from Acanthella cavernosa in 2000. The same structure 1 was later reported by Wright et al. from the nudibranch Phyllidiella pustulosa and its sponge diet, but with different NMR data. The syntheses of both enantiomers of 1 were accomplished through the isothiocyanation of 10-isocyano-4-cadinene (2) previously synthesized by our group. The correct spectroscopic data and specific rotation value of the structure 1 were determined on the basis of the syntheses. The NMR data of synthetic 1 matched those of the isothiocyanate isolated by Garson and differed from those reported by Wright. The spectroscopic data and specific rotation values of 10-epi-10-isothiocyanato-4-cadinene (6) and di-1,6-epi-10-isothiocyanato-4-cadinene (8) were also established through the syntheses of these diastereomers. Structure 6 has been reported as a natural product by Mitome et al., but the NMR data for the synthetic sample of 6 differ from those of the natural isolate.
  • 梅澤 大樹, 清野 智也, 松田 冬彦
    天然有機化合物討論会講演要旨集 54 297 - 302 天然有機化合物討論会 2012年09月01日 
    Horner-Wadsworth-Emmons reaction (HWE reaction) is known as a reliable and powerful method for carbon-carbon bond formation by coupling between β-ketophosphonate and aldehyde to give α,β-unsaturated compound with high stereoselectivity. In general, the β-ketophosphonate used as the HWE reaction precursor is needed to be synthesized from a readily accessible material. However, these procedures sometimes encounter troubles in purification due to its high polarity or side products. To avoid these problems, we planned one-pot synthesis of the α,β-unsaturated ketone with aldehyde, acyl fluoride and trimethylsilylmethylphosphonate through HWE reaction according to the sequential reaction illustrated in Scheme 1. The reaction conditions were optimized by examining bases, reaction time, and equivalent of reagents as shown in Table 1. With the optimized conditions (Table 1. Entry 7), wide variety of substrates (aldehyde, acyl fluoride, and phosphonate) bearing various functional groups were coupled to give α,β-unsaturated ketone in high yields with E geometry. (Table 2) Z-α,β-Unsaturated ketones were also prepared with high stereoselectivity by using one-pot procedure. (Table 3)
  • Andrea Roxanne J. Anas, Takaya Kisugi, Taiki Umezawa, Fuyuhiko Matsuda, Marc R. Campitelli, Ronald J. Quinn, Tatsufumi Okino
    JOURNAL OF NATURAL PRODUCTS 75 9 1546 - 1552 2012年09月 [査読有り][通常論文]
     
    Bioassay-guided investigation of the cyanobacterium Anabaena compacta extracts afforded spumigin J (1) and the known thrombin inhibitor spumigin A (2). The absolute configuration of 1 was analyzed by advanced Marfey's methodology. Compounds 1 and 2 inhibited thrombin with EC50 values of 4.9 and 2.1 mu M, and 0.7 and 0.2 mu M in the cathepsin B inhibitory assay, respectively. The MM-GBSA methodology predicted spumigin A with 2S-4-methylproline as the better thrombin inhibitor.
  • Taiki Umezawa, Tomoya Seino, Fuyuhiko Matsuda
    ORGANIC LETTERS 14 16 4206 - 4209 2012年08月 [査読有り][通常論文]
     
    A novel three-component coupling between trimethylsilylmethylphosphonate, acyl fluoride, and aldehyde has been developed. A sequential nucleophilic addition of lithio-trimethylsilylmethylphosphonate to the acyl fluoride and Horner-Wadsworth-Emmons reaction of an aldehyde with the lithio-beta-ketophosphonate generated in situ by desilylation at the alpha-position of the alpha-silyl-beta-ketophosphonate by fluoride took place cleanly in a one-pot operation. Various E- and Z-enones were obtained in high yields with high stereoselectivities by this one-pot procedure.
  • Taiki Umezawa, Manabu Sueda, Takao Kamura, Teppei Kawahara, Xuerong Han, Tatsufumi Okino, Fuyuhiko Matsuda
    JOURNAL OF ORGANIC CHEMISTRY 77 1 357 - 370 2012年01月 [査読有り][通常論文]
     
    Total syntheses of kalkitoxin, isolated from the Caribbean Lyngbya majuscula, and its analogues, 3-epi-, 7-epi-, 8-epi-, 10-epi-, 10-nor-, and 16-nor-kalldtcocin, were achieved via oxazolidinone-based diastereoselective 1,4-addition reaction of a methyl group and efficient T1C14-mediated thiazoline ring formation as the key steps. The biological activities of synthetic kalkitoxin and its analogues were evaluated with brine shrimp.
  • 梅澤 大樹, 柴田 昌幸, 松田 冬彦
    天然有機化合物討論会講演要旨集 52 1 - 6 天然有機化合物討論会 2010年09月01日 
    Danicalipin A (1), a major component of chlorosulfolipids (CSLs) from Ochromonas danica, was first isolated more than four decades ago along wigh its congeners 2-6. Although the planar structure of 1 was reorted in 1973, the absolute and relative stereochemistries of 1 have not been determined until 2009; total synthesis by Vanderwal and NMR analysis of natural sample by Okino. Due to the unprecedent structure of CSLs, CSLs have attracted much attention of synthetic chemists and total syntheses of 1, 7, and 8 were achieved by three groups. In this presentation, asymmetric total synthesis of Danicalipin A (1) will be described. The synthesis commenced with the known optically active epoxide 14, derived via Sharpless-Katsuki asymmetric epoxidation, which was transformed into the α,β-unsaturated ester 15. (Scheme 2) At this stage, the enantiomeric excess of 15 was enhanced from 85% ee to >99% ee by recrystallization. Four transformations involving regioselective epoxy opening reaction gave the aldehyde 13. After diastereoselective α-chlorination of 13 with 19, the aldehyde 10 was synthesized in 2 steps. Wittig reaction between 10 and the phosphonium salt 11, derived from the known aldehyde 12, afforded the alkene 24. E-olefin for the trans-dichloride at C15 and 16 was installed by Wiitg olefination, furnishing the α,β-unsaturated ester 26. After introduction of n-hexyl group from ester, trans addition of chlorine equivalent into E-olefin at 80℃ gave the adduct 29, which was successfully converted to Danicalipin A.
  • 梅澤 大樹, 香村 隆夫, 河原 哲平, 末田 学, 韓 雪容, 沖野 龍文, 松田 冬彦
    天然有機化合物討論会講演要旨集 51 329 - 334 天然有機化合物討論会 2009年09月01日 
    Kalkitoxin (1) was isolated from cyanobacterium Lyngbya majuscule in the Caribbean Sea. It is reported that 1 posssesses some intersting biological activities. For example, 1 shows a strong ichtyotoxic activity toward the common gold fish and brine shrimp. Also, kalkitoxin has a strong neurotoxicity (LC_<50>=3.86nM) in cerebellar granule neouron (CGN) as an inhibitor N-methyl-D-aspartate (NMDA) receptor antagonists and is a highly potent blocker of the voltage-depending sodium channel in mouse neuro-2a cells (EC_<50>=1nM). We have been attracted by the structure-activity relationship of kalkitoxins. In present paper, we describe the synthesis of kalkitoxin and its analogues (epimer and demethylated kalkitoxins (nor form) and their biological activity with brine shrimp. The synthesis was started from 15, which was converted to α,β-unsaturaed imide 14 with phosphonate 17. 1,4-Addition reaction to 14 with methyl curprate gave imide 18 as 10 : 1 mixture of diastereomers. The imide 18 was transformed into second 1,4-addition precursor 11 in 9 steps. The conjugate addition reaction of 11 proceeded smoothly to give imide 26 as a single diastereomer, which was derived to 1 via condensation with amine 10, synthesize without racemization by novel method, and highly efficient thiazoline formation with TiCl_4. Kalkitoxin analogues 2-7 were synthesized in the similar manner by simply changing the chiral auxiliary or chiral building block. Finally, the biological activity with 1-7 was evaluated as LC_<50> toward brine shrimp.
  • 西川 慶祐, 代蔵 陽介, 中原 博史, 梅澤 大樹, 松田 冬彦
    天然有機化合物討論会講演要旨集 50 777 - 782 天然有機化合物討論会 2008年09月01日 
    10-Isocyano-4-cadinene (1), a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae by Okino et al., exhibits potent antifouling activity against the larvae of the barnacle Balanus amphitrite (EC_<50> 0.14μg/mL). 10-Isocyano-4-cadinene (1) is expected to be new nontoxic antifouling agents. Furthermore, the absolute stereochemistry of 1 has not been determined. To access these issues, we started the enantioselective total synthesis toward 1. The synthesis toward 1 was commenced with known imide 6, which was converted into dieneacetate 5c in 9 steps. The Diels-Alder reaction between 5c and methyl acrylate with MeAlCl_2 afforded cyclohexene 11c as a mixture of four diasereomers. This mixture was epimerized to two isomers, desired carboxylic acid 12 as a major product and ester 13, by the treatment of NaOMe followed by selective hydrolysis with 1N HCl in one-pot. Carboxylic acid 12 was transformed into aldehyde 14, which was cyclized by SmI_2-induced Barbier-type reaction to give alcohol 15. To introduce the functional groups at C10, homologation of 15 with TosMIC afforded aldehyde 16, which was treated with t-BuOK and 21 to give MPM ether 22 in stereoselective fashion. Wolff-Kishner reaction followed by Curtis rearrangement of 24 gave isocyanate 25, C10 was fully functionalized. Total synthesis was completed by reduction of isocyano group with NaBH_4 and dehydration with POCl_3. The absolute configuration of 1 was determined as (1R, 6R, 7S, 10R) by the comparison with the optical rotation between natural and synthetic samples.

作品等

  • 若手研究者のための有機合成セミナー
    2008年

その他活動・業績

  • 梅澤大樹, 長谷川裕己, SARI Ira Novita, 鈴木惇也, 諸角達也, 野方靖行, 吉村えり奈, 松田冬彦 マリンバイオテクノロジー学会大会講演要旨集 19th 80 2017年06月03日 [査読無し][通常論文]
  • 梅澤大樹, 長谷川裕己, SARI Ira Novita, 鈴木惇也, 諸角達也, 松田冬彦, 野方靖行, 吉村えり奈 Sessile Organisms 34 (2) 2017年
  • Taiki Umezawa, Akinori Sato, Yasuto Ameda, Loida O. Casalme, Fuyuhiko Matsuda TETRAHEDRON LETTERS 56 (1) 168 -171 2015年01月 [査読無し][通常論文]
     
    A convenient and scalable synthesis of two unusual amino acid units found in dolastatin 16, dolaphenvaline, and dolamethylleuine, is described. Dolastatin 16, which was first isolated from the sea hare Dolabella auricularia by Pettit, exhibits not only strong inhibition of growth for a variety of human cancer cell lines but also potent antifouling activity against the larvae of the barnacle Balanus amphitrite. The key element of the synthesis is an organocatalytic Mannich reaction to construct two contiguous stereocenters in the amino acid units with almost complete enantio- and diastereoselectivity. (C) 2014 Elsevier Ltd. All rights reserved.
  • Taiki Umezawa, Fuyuhiko Matsuda TETRAHEDRON LETTERS 55 (19) 3003 -3012 2014年05月 [査読無し][通常論文]
     
    Chlorosulfolipids (CSLs) are an intriguing family of natural products featuring highly chlorinated linear hydrocarbon skeletons. Although CSLs were first isolated in 1962, chemical synthesis of CSLs was hampered because relevant methods for stereoselective construction of the polychlorinated motifs of CSLs were scarce. Since Carreira's first total synthesis of the CSL mytilipin A in 2009, several groups, including our own, have reported total syntheses of CSLs. As a result of these total syntheses, important progress has been made in the development of reliable synthetic methods for stereoselective polychlorination. In this digest, we summarize the total syntheses of CSLs by focusing on synthetic methods for stereoselective polychlorination of the organic frameworks of CSLs. (c) 2014 Published by Elsevier Ltd.
  • 金子賢介, 鷲尾健司, 梅澤大樹, 松田冬彦, 森川正章, 沖野龍文 日本水産学会大会講演要旨集 2014 119 2014年03月27日 [査読無し][通常論文]
  • 前田武志, 梅澤大樹, 松田冬彦 日本化学会講演予稿集 94th (4) 1492 2014年03月12日 [査読無し][通常論文]
  • 佐藤彰則, 梅澤大樹, 松田冬彦 日本化学会講演予稿集 94th (4) 1468 2014年03月12日 [査読無し][通常論文]
  • 梅澤大樹 上原記念生命科学財団研究報告集(CD-ROM) 27 ROMBUNNO.11 2013年12月10日 [査読無し][通常論文]
  • 金子賢介, 鷲尾健司, 梅澤大樹, 松田冬彦, 森川正章, 沖野龍文 マリンバイオテクノロジー学会大会講演要旨集 15th 68 2013年06月01日 [査読無し][通常論文]
  • 梅澤大樹, 清野智也, 松田冬彦 日本化学会講演予稿集 93rd (4) 1202 2013年03月08日 [査読無し][通常論文]
  • 梅澤大樹, 清野智也, 松田冬彦 日本化学会講演予稿集 92nd (4) 1156 2012年03月09日 [査読無し][通常論文]
  • 梅澤 大樹, 松田 冬彦 有機合成化学協会誌 69 (10) 1122 -1133 2011年10月 [査読無し][通常論文]
     
    Chlorosulfolipids (CSLs) represent an unusual family of natural products that were first isolated from the freshwater alga Ochromonas danica in the 1960s. They have drawn considerable attention as substances of toxicological concern, because some of them display modest cytotoxic activity and are associated with seafood poisoning. CSLs are unique in featuring hydrocarbon framework which possess chlorine-substituted multiple stereogenic centers. Due to the unprecedented structure and interesting biological activity of CSLs, this fascinating class of natural products has recently garnered interest as targets of total synthesis and inspired methodology for stereoselective chlorination. In 2009, Carreira accomplished the total synthesis of hexachlorosulfolipid. After this total synthesis, other three groups including our group have achieved total syntheses of CSLs: Malhamensilipin A and danicalipin A by Vanderwal, hexachlorosulfolipid and danicalipin A by Yoshimitsu and Tanaka, and danicalipin A by authors. This review deals with these total syntheses of CSLs, focusing the development of synthetic methods to stereoselectively incorporate acyclic polychlorinated arrays into hydrocarbon skeletons of CSLs.
  • Taiki Umezawa, Fuyuhiko Matsuda Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 69 (10) 1122 -1133 2011年10月 [査読無し][通常論文]
     
    Chlorosulfolipids (CSLs) represent an unusual family of natural products that were first isolated from the freshwater alga Ochromonas danica in the 1960s. They have drawn considerable attention as substances of toxicological concern, because some of them display modest cytotoxic activity and are associated with seafood poisoning. CSLs are unique in featuring hydrocarbon framework which possess chlorine-substituted multiple stereogenic centers. Due to the unprecedented structure and interesting biological activity of CSLs, this fascinating class of natural products has recently garnered interest as targets of total synthesis and inspired methodology for stereoselective chlorination. In 2009, Carreira accomplished the total synthesis of hexachlorosulfolipid. After this total synthesis, other three groups including our group have achieved total syntheses of CSLs: Malhamensilipin A and danicalipin A by Vanderwal, hexachlorosulfolipid and danicalipin A by Yoshimitsu and Tanaka, and danicalipin A by authors. This review deals with these total syntheses of CSLs, focusing the development of synthetic methods to stereoselectively incorporate acyclic polychlorinated arrays into hydrocarbon skeletons of CSLs.
  • 梅澤大樹, 鈴木将洋, 小栗祐子, 松浦裕志, 沖野龍文, 松田冬彦 天然有機化合物討論会講演要旨集 53rd 637 -642 2011年09月02日 [査読無し][通常論文]
  • 梅澤大樹 化学と工業 64 (9) 688 -689 2011年09月01日 [査読無し][通常論文]
  • Keisuke Nishikawa, Hiroshi Nakahara, Yousuke Shirokura, Yasuyuki Nogata, Erina Yoshimura, Taiki Umezawa, Tatsufumi Okino, Fuyuhiko Matsuda JOURNAL OF ORGANIC CHEMISTRY 76 (16) 6558 -6573 2011年08月 [査読無し][通常論文]
     
    The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, and determination of its absolute stereochemistry were achieved. 10-Isocyano-4-cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, intermolecular Diels-Alder reaction and samarium diiodide induced Barbier-type cyclization were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined as (1S,6S,7R,10S) by comparison of the optical rotations between natural and synthetic samples. In addition, the authors successfully synthesized 10-epi- and di-1,6-epi-10-isocyano-4-cadinene through the same synthetic pathway. Antifouling activities against Balanus amphitrite with the cadinenes were also evaluated.
  • Taiki Umezawa, Masayuki Shibata, Kensuke Kaneko, Tatsufumi Okino, Fuyuhiko Matsuda ORGANIC LETTERS 13 (5) 904 -907 2011年03月 [査読無し][通常論文]
     
    Asymmetric total synthesis of danicalipin A was achieved. The synthesis was characterized by diastereoselective introduction of chlorine atoms. Biological activities with synthetic danicalipin A, its enantiomer, and racemate were also evaluated toward brine shrimp. Both enantiomers of danicalipin A showed almost the same activity.
  • Taiki Umezawa, Tetsuro Shinada, Yasufumi Ohfune CHEMISTRY LETTERS 39 (12) 1281 -1282 2010年12月 [査読無し][通常論文]
     
    The synthesis of (1) C-labeled 5,6,11-trideoxytetrodotoxin has been successfully achieved This is the first example of the C-13-labeled analogs in tetrodotoxin congeners
  • Tetsuro Shinada, Makoto Hamada, Kota Miyoshi, Masato Higashino, Taiki Umezawa, Yasufumi Ohfune SYNLETT (14) 2141 -2145 2010年09月 [査読無し][通常論文]
     
    K2HPO4 is an efficient catalyst for the transesterification reaction to produce methyl esters. Various functional groups are compatible under the mild reaction conditions.
  • K. C. Nicolaou, Christine F. Gelin, Jae Hong Seo, Zhihong Huang, Taiki Umezawa JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 132 (28) 9900 -9907 2010年07月 [査読無し][通常論文]
     
    A devised synthetic strategy toward the QRSTU ring system 4 of the marine-derived biotoxin maitotoxin (1) delivered, in addition to 4, its diastereoisomers 85-epi-QRSTU and 86-epi-QRSTU ring systems 5 and 6. The convergent route to these maitotoxin fragments involved coupling of UT and Q building blocks 9 (obtained from 2-deoxy-D-ribose) and 10 (obtained from D-ribose) followed by ring-closing metathesis to afford enol ether 8, whose elaboration to the targeted QRSTU ring system 4 required its conversion to hydroxy ketone 7. The latter compound (7) was transformed to the final product through a hydroxy dithioketal cyclization, followed by oxidation/methylation of the resulting O,S-mixed ketal to install the last of the five methyl groups contained within the target molecule (4). (13)C NMR spectroscopic analysis of synthesized fragments 4, 5, and 6 and comparisons with maitotoxin provided strong support for the originally assigned structure of the QRSTU domain of the natural product.
  • 西川慶祐, 代蔵陽介, 野方靖行, 吉村えり奈, 梅澤大樹, 沖野龍文, 松田冬彦 日本化学会講演予稿集 90th (4) 1043 2010年03月12日 [査読無し][通常論文]
  • Keisuke Nishikawa, Hiroshi Nakahara, Yousuke Shirokura, Yasuyuki Nogata, Erina Yoshimura, Taiki Umezawa, Tatsufumi Okino, Fuyuhiko Matsuda ORGANIC LETTERS 12 (5) 904 -907 2010年03月 [査読無し][通常論文]
     
    The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine sesquiterpene isolated from nudibranchs of the family Phyllidiidae, was achieved. The cadinene is expected to be a novel nontoxic antifouling agent. In the synthesis, an intermolecular Diels-Alder reaction and a SMl(2)-induced Barbier-type reaction were employed as key steps. The absolute configuration of 10-isocyano-4-cadinene was determined to be (1S, 6S, 7R, 10S) on the basis of the total synthesis. Antifouling activities against Balanus amphitrite with both enantiomers of 10-isocyano-4-cadinene were also evaluated.
  • 松田 冬彦, 梅澤 大樹 ファルマシア 44 (10) 959 -964 2008年10月01日
  • K. C. Nicolaou, Michael O. Frederick, Antonio C. B. Burtoloso, Ross M. Denton, Fatima Rivas, Kevin P. Cole, Robert J. Aversa, Romelo Gibe, Taiki Umezawa, Takahiro Suzuki JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 130 (23) 7466 -7476 2008年06月 [査読無し][通常論文]
     
    As the largest secondary metabolite to be discovered as of yet, the polyether marine neurotoxin maiitotoxin constitutes a major structural and synthetic challenge. After its originally proposed structure (1) had been questioned on the basis of biosynthetic considerations, we provided computational and experimental support for structure 1. In an effort to provide stronger experimental evidence of the molecular architecture of maitotoxin, its GHIJKLMNO ring system 21 was synthesized. The (13)C NMR chemical shifts of synthetic 3 matched closely those corresponding to the same domain of the natural product providing strong evidence for the correctness of the originally proposed structure of maitotoxin (1).
  • Taiki Umezawa, Toshihiro Hayashi, Hiroshi Sakai, Hidetoshi Teramoto, Takeshi Yoshikawa, Masashi Izumida, Yoshinori Tamatani, Tadashi Hirose, Yasufumi Ohfune, Tetsuro Shinada ORGANIC LETTERS 8 (21) 4971 -4974 2006年10月 [査読無し][通常論文]
     
    The first total synthesis of 5,6,11-trideoxytetrodotoxin (1) and its 4-epimer were achieved. The synthesis is characterized by the stereoselective construction of the quaternary amino carbon center at C8a by an asymmetric transferring Strecker synthesis and the highly efficient conversion of cyanohydrin 4 to 1 via intramolecular cyclization reactions.
  • Shinada Tetsuro, Umezawa Taiki, Hayashi Toshihiro, Sakai Hiroshi, Kawakami Tadashi, Teramoto Hidetoshi, Yoshikawa Takeshi, Izumida Masashi, Tamatani Yoshinori, Hirose Tadashi, Ohfune Yasufumi International Symposium on the Chemistry of Natural Products 2006 "P -107" 2006年07月23日 [査読無し][通常論文]
  • Kozuma Hayato, Umezawa Taiki, Ando Takeshi, Shinada Tetsuro, Ohfune Yasufumi International Symposium on the Chemistry of Natural Products 2006 "P -216" 2006年07月23日 [査読無し][通常論文]
  • Tetsuro Shinada, Tadashi Kawakami, Hiroshi Sakai, Hiromi Matsuda, Taiki Umezawa, Masaki Kawasaki, Kosuke Namba, Yasufumi Ohfune BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 79 (5) 768 -774 2006年05月 [査読無し][通常論文]
     
    Stereoselective synthesis of both optically active cis- and trans-1-amino-2-hydroxycyclohexane-1-carboxylic acids (Ahhs) 1a and 1b was accomplished by an asymmetric version of the Strecker synthesis. Stereochemical aspects of their chiral induction processes are investigated.
  • Tetsuro Shinada, Tadashi Kawakami, Hiroshi Sakai, Hiromi Matsuda, Taiki Umezawa, Masaki Kawasaki, Kosuke Namba, Yasufumi Ohfune BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 79 (5) 768 -774 2006年05月 [査読無し][通常論文]
     
    Stereoselective synthesis of both optically active cis- and trans-1-amino-2-hydroxycyclohexane-1-carboxylic acids (Ahhs) 1a and 1b was accomplished by an asymmetric version of the Strecker synthesis. Stereochemical aspects of their chiral induction processes are investigated.
  • SHINADA Tetsuro, UMEZAWA Taiki, ANDO Tsuyoshi, KOZUMA Hayato, OHFUNE Yasufumi Tetraheron Letters 47 (12) 1945 -1947 2006年03月 [査読無し][通常論文]
     
    An efficient synthesis of N-acyl-N'-substituted guanidines by condensation reaction of thiourea and (Me3Si)(2)NH in the presence of EDCI is described. Various guanidines were synthesized in a simple manner. (c) 2006 Elsevier Ltd. All rights reserved.
  • 梅澤 大樹, 品田 哲郎, 大船 泰史 天然有機化合物討論会講演要旨集 47 (0) 77 -82 2005年 [査読無し][通常論文]
     
    Tetrodotoxin (TTX) is a toxic principle of puffer fish poisoning. TTX is a useful biological tool because of its specificity for blocking voltage-dependent sodium channels. 5,6,11-Trideoxy TTX (1), one of the congeners of TTX, has also been isolated from ovaries of puffers, Fugu poecilonotus, by Yasumoto et al. in 1995 and received significant interests in view of biosynthetic relationship with TTX. Synthetic studies of TTX and its congeners have been extensive due to their biological activities as well as their molecular complexity consisting of a quaternary carbon center attached to an amino group, concomitant polyol system, a cyclic guanidine containing an aminal, and an ortho acid for TTX or a δ-lactone for some of the congeners. In this report, we wish to describe the first total synthesis of 5,6,11-trideoxy TTX (1) and its 4-epimer 2. The synthesis was commenced with the known triol 7, prepared from (-)-quinic acid in 4 steps, which was converted to Strecker precursor 6 in 6 steps. 6 was subjected to an asymmetric transferring Strecker synthesis for the diastereoselective construction of a quaternary carbon center involving an amino group at C8a. Installation of a hydroxy group to C7 was accomplished by the Mislow-Evans rearrangement to give 20. Initial hydrogenation of 20 for the introduction of β-methyl group at C6 and subsequent pyrrolidine ring opening via lactam 24 gave alcohol 25. The hydroxyethyl group of 25 was transformed to a vinyl group in 3 steps to give 26. Inversion of the hydroxy group at C7 was performed by oxidation to a diketone followed by diastereoselective reduction to give cis-diol 4, This was converted to aldehyde 28, which, upon treatment with TMSCN in the presence of Et_3N, gave a cyanohydrin as an inseparable mixture of diastereomers. The mixture was guanidylated to give 29. Ozonolysis of the desired (9S)-29 followed by exposure to 20% TFA afforded a mixture of 5,6,11-trideoxyTTX (1), and its 4-epimer 2 and anhydro derivative 31. Thus, the total syntheses of 1 and 2 were accomplished.

共同研究・競争的資金等の研究課題

  • 環境にやさしい付着阻害剤の開発を指向した天然物誘導体合成と付着阻害メカニズム解明
    科研費:基盤研究(B)
    研究期間 : 2018年04月 -2022年03月 
    代表者 : 梅澤 大樹
  • 海洋生物の防御機能を模倣したバイオマス循環型船底付着阻害剤の合成的探索研究
    環境省:環境総合研究推進費
    研究期間 : 2016年04月 -2018年03月 
    代表者 : 梅澤 大樹
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2015年 -2016年 
    代表者 : 梅澤 大樹
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2011年 -2012年 
    代表者 : 梅澤 大樹
     
    研究実施計画に基づいて、クロロスルフォリピッドを合成するための2つのフラグメントの合成、およびそれらをカップリングするための反応条件についても併せて検討した。各種検討の結果、2つのフラグメントのうちの1つの効率的な合成法をほぼ確立するとともに、もう片方のフラグメントを効率的に合成するための新規合成方法論(アルデヒド、トリメチルシリルメチルホスホネート、酸フッ化物を用いた3成分カップリング)を確立することに成功した。この合成方法論は、様々な官能基を有する化合物に対して適用でき、各種有機化合物を合成するために有用な方法であり、この方法を用いた天然有機化合物合成へと応用することも可能である。本合成方法論は、OrganicLetters誌にて報告した。クロロスルフォリピッド本体の合成については、合成したフラグメントをカップリングするため、モデル化合物による検討をすすめている。

教育活動情報

主要な担当授業

  • 生体物質科学特論Ⅱ
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 環境科学院
    キーワード : 天然物化学、化学生態学 Natural Product Chemistry, Chemical Ecology
  • 化学Ⅱ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 有機化合物、官能基、分子構造、化学的性質、化学反応、機能性有機物、生体関連有機物質


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