2016年10月, 平成27年度「日本化学会北海道支部奨励賞」　　　　　　　　　　　　　　　

Doubly Homologated Tyrosine-Containing Peptides from the Cyanobacterium Microcystis aeruginosa NIES-4285 and Their Biosynthesis
Chin-Soon Phan, Zhengyi Ling, Jakia Jerin Mehjabin, Kenichi Matsuda, Nurcahyo Iman Prakoso, Taiki Umezawa, Toshiyuki Wakimoto, Tatsufumi Okino
Journal of Natural Products, American Chemical Society (ACS), 2024年10月30日
研究論文（学術雑誌）

Distinct regulation of two flagella by calcium during chemotaxis of male gametes in the brown alga Mutimo cylindricus (Cutleriaceae, Tilopteridales)
Kinoshita‐Terauchi N, Shiba K, Umezawa T, Inaba K
Journal of phycology, 2024年04月
研究論文（学術雑誌）

Mild Metal-Free 1,2-Dichlorination of Alkynes by NCS-PPh3-H2O System
Jianan Yuan, Nurcahyo Iman Prakoso, Tatsuya Morozumi, Taiki Umezawa
Synthesis (Germany), 56, 5, 771, 776, 2023年09月15日
研究論文（学術雑誌）, Facile dichlorination of alkynes to give 1,2-dichloroalkenes is described. Previous studies for the synthesis of the 1,2-dichloro-alkenes from the corresponding alkynes require stoichiometric amount of copper salt, preparation of the chlorinating reagent from hazardous compounds such as molecular chlorine, and highly acidic conditions. In this paper, only ubiquitous reagents, NCS-PPh3-H2O, are used to prepare the 1,2-dichloroalkenes from the alkynes under mild conditions. Various functional groups such as esters, ethers or carbamates were tolerated under these reaction conditions.

Formation pathway by by-products in methacrolein oxidation over H3PMo12O40 investigated by using 12C-labeled methacrolein
Mitsuru Kanno, Jun Hirata, Taiki Umezawa, Wataru Ninomiya, Yuichi Kamiya
Journal of the Japan Petroleum Institute, 66, 4, 128, 131, Japan Petroleum Institute, 2023年07月01日, ［査読有り］
英語, 研究論文（学術雑誌）

Syntheses and Biological Activities of Danicalipin A Derivatives.
Taiki Umezawa, Takeshi Maeda, Takuya Akiyama, Nurcahyo Iman Prakoso, Jakia Jerin Mehjabin, Tatsufumi Okino, Fuyuhiko Matsuda
Chemistry & biodiversity, 20, 6, e202300400, 2023年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Synthesis of three derivatives of danicalipin A, tetrachloride, trisulfate and a fluorescent probe was achieved through Wittig reaction strategy. Toxicity of the derivatives against brine shrimp (Artemia salina) as also investigated to provide useful information for the biological activity; i) less chloride derivative showed similar toxicity to danicalipin A, ii) the amphiphilic property, a characteristic feature of danicalipin A, was crucial because trisulfate considerably decreased the toxicity and iii) fluorescent derivative kept brine shrimp toxicity of danicalipin A.

Scope and limitations of absolute configuration determination of allenic natural products using the CCC stretching VCD signal.
Tohru Taniguchi, Mutmainah, Shu Takimoto, Takahiro Suzuki, Soichiro Watanabe, Fuyuhiko Matsuda, Taiki Umezawa, Kenji Monde
Organic & biomolecular chemistry, 21, 3, 569, 574, Royal Society of Chemistry ({RSC}), 2023年01月18日, ［国際誌］
英語, 研究論文（学術雑誌）, The allene functional group in natural products isolated so far exists in a non-racemic form, but its axial chirality is difficult to elucidate. Allenes exhibit a characteristic antisymmetric CCC stretching mode at around 1950 cm-1, and their VCD properties have not been studied in detail. This work, for the first time, applied VCD spectroscopy to allenic natural products and allenic molecules with other asymmetric centers focusing on the antisymmetric CCC stretching mode. This vibrational mode yielded a negligibly weak VCD signal for several molecules, but in the presence of electron-withdrawing and/or conjugating substituents, it generated a stronger one. Its sign was found to be influenced by the nature of substituents. These findings should deepen the understanding of the VCD properties of the allene functional group and should be useful for future studies of chiral allenes.

Model Study toward Total Synthesis of Mytilipin C
Taiki Umezawa, Nurcahyo Iman Prakoso, Koichi Tsuji, Yosuke Ogura, Takumi Sato, Fuyuhiko Matsuda
Bulletin of the Chemical Society of Japan, 95, 10, 1491, 1500, The Chemical Society of Japan, 2022年10月15日
英語, 研究論文（学術雑誌）

Nostosin G and Spiroidesin B from the Cyanobacterium Dolichospermum sp. NIES-1697
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, American Chemical Society (ACS), 2022年08月10日
研究論文（学術雑誌）

Enantioselective Total Synthesis of Multifidene, a Sex Pheromone of Brown Algae
Taiki Umezawa, Misaki Hara, Nana Kinoshita-Terauchi, Fuyuhiko Matsuda
Organics, 3, 3, 187, 195, MDPI AG, 2022年07月
研究論文（学術雑誌）, 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.

Effective Synthesis and Antifouling Activity of Dolastatin 16 Derivatives.
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, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Efficient synthesis of α,β-dichlorinated ketones from α,β-dichlorinated Weinreb amides through a simple work-up procedure.
Nurcahyo Iman Prakoso, Fuyuhiko Matsuda, Taiki Umezawa
Organic & biomolecular chemistry, 19, 36, 7822, 7826, ROYAL SOC CHEMISTRY, 2021年09月22日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Assignment of Absolute Configuration of Bromoallenes by Vacuum-Ultraviolet Circular Dichroism (VUVCD).
Taiki Umezawa, Nakaba Mizutani, Koichi Matsuo, Yuugo Tokunaga, Fuyuhiko Matsuda, Tatsuo Nehira
Molecules (Basel, Switzerland), 26, 5, MDPI, 2021年02月27日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Biosurfactants from Marine Cyanobacteria Collected in Sabah, Malaysia
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, American Chemical Society (ACS), 2020年05月20日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

A Reliable Method to Create Adjacent Acid-Base Pair Sites on Silica through Hydrolysis of Pre-anchored Amide
Wontae Kim, Loida O. Casalme, Taiki Umezawa, Fuyuhiko Matsuda, Ryoichi Otomo, Yuichi Kamiya
Chemistry Letters, 49, 1, 71, 74, The Chemical Society of Japan, 2020年01月05日
研究論文（学術雑誌）

Neighboring Effect of Intramolecular Chlorine Atoms on Epoxide Opening Reaction by Chloride Anions.
Taiki Umezawa, Masayuki Shibata, Ryutaro Tamagawa, Fuyuhiko Matsuda
Organic letters, 21, 19, 7731, 7735, AMER CHEMICAL SOC, 2019年10月04日, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

A brown algal sex pheromone reverses the sign of phototaxis by cAMP/Ca-dependent signaling in the male gametes of Mutimo cylindricus (Cutleriaceae)
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］
英語, 研究論文（学術雑誌）, 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

A brown algal sex pheromone reverses the sign of phototaxis by cAMP/Ca2+-dependent signaling in the male gametes of Mutimo cylindricus (Cutleriaceae)
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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Synthesis and Structure-Activity Relationship of Omaezallene Derivatives.
Taiki Umezawa, Nurcahyo Iman Prakoso, Miho Kannaka, Yasuyuki Nogata, Erina Yoshimura, Tatsufumi Okino, Fuyuhiko Matsuda
Chemistry & biodiversity, 16, 1, e1800451, WILEY-V C H VERLAG GMBH, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Total synthesis of omaezallene toward structure determination
Taiki Umezawa
Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 76, 5, 426, 429, Society of Synthetic Organic Chemistry, 2018年, ［査読有り］
日本語, 研究論文（学術雑誌）, 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.

Antioxidants from the brown alga dictyopteris undulata
Momochika Kumagai, Keisuke Nishikawa, Hiroshi Matsuura, Taiki Umezawa, Fuyuhiko Matsuda, Tatsufumi Okino
Molecules, 23, 5, MDPI AG, 2018年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Serinolamides and Lyngbyabellins from an Okeania sp Cyanobacterium Collected from the Red Sea
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, AMER CHEMICAL SOC, 2017年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Total synthesis of (-)-kainic acid and (+)-allo-kainic acid through SmI₂-mediated intramolecular coupling between allyl chloride and an α,β-unsaturated ester.
Suzuki J, Miyano N, Yashiro S, Umezawa T, Matsuda F
Organic & biomolecular chemistry, 15, 31, 6557, 6566, ROYAL SOC CHEMISTRY, 2017年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Columbamides D and E: Chlorinated Fatty Acid Amides from the Marine Cyanobacterium Moorea bouillonii Collected in Malaysia
Julius Adam V. Lopez, Julie G. Petitbois, Charles S. Vairappan, Taiki Umezawa, Fuyuhiko Matsuda, Tatsufumi Okino
ORGANIC LETTERS, 19, 16, 4231, 4234, AMER CHEMICAL SOC, 2017年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Design, Synthesis, and Antifouling Activity of Glucosamine-Based Isocyanides
Taiki Umezawa, Yuki Hasegawa, Ira S. Novita, Junya Suzuki, Tatsuya Morozumi, Yasuyuki Nogata, Erina Yoshimura, Fuyuhiko Matsuda
MARINE DRUGS, 15, 7, MDPI AG, 2017年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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).

Total synthesis and biological activity of dolastatin 16
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, ROYAL SOC CHEMISTRY, 2017年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

EFFECT OF SEX PHEROMONE ON THE SIGN OF PHOTOTAXIS IN BROWN ALGAL MALE GAMETES
Taiki Umezawa
Phycologia, 2017年
研究論文（学術雑誌）

Total Synthesis of Natural Antifouling Products
Taiki Umezawa, Keisuke Nishikawa, Tatsufumi Okino, Fuyuhiko Matsuda
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 74, 7, 689, 699, SOC SYNTHETIC ORGANIC CHEM JPN, 2016年07月, ［査読有り］
日本語, 研究論文（学術雑誌）, 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.

Synthetic study on dolastatin 16: concise and scalable synthesis of two unusual amino acid units
Taiki Umezawa, Akinori Sato, Yasuto Ameda, Loida O. Casalme, Fuyuhiko Matsuda
TETRAHEDRON LETTERS, 56, 1, 168, 171, PERGAMON-ELSEVIER SCIENCE LTD, 2015年01月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

cDNA cloning and characterization of vanadium-dependent bromoperoxidases from the red alga Laurencia nipponica
Kensuke Kaneko, Kenji Washio, Taiki Umezawa, Fuyuhiko Matsuda, Masaaki Morikawa, Tatsufumi Okino
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 78, 8, 1310, 1319, TAYLOR & FRANCIS LTD, 2014年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Recent progress toward synthesis of chlorosulfolipids: total synthesis and methodology
Taiki Umezawa, Fuyuhiko Matsuda
TETRAHEDRON LETTERS, 55, 19, 3003, 3012, PERGAMON-ELSEVIER SCIENCE LTD, 2014年05月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Omaezallene from Red Alga Laurencia sp.: Structure Elucidation, Total Synthesis, and Antifouling Activity
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, WILEY-V C H VERLAG GMBH, 2014年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

紅藻ソゾ属Laurenciaのブロモペルオキシダーゼ
金子 賢介, 鷲尾 健司, 梅澤 大樹, 小林 大毅, 湯 暁蓉, 松田 冬彦, 森川 正章, 沖野 龍文
天然有機化合物討論会講演要旨集, 56, Poster53, 天然有機化合物討論会実行委員会, 2014年
日本語, 紅藻ウラソゾ (Laurencia nipponica) から含臭素環状エーテル laurencin (1) が単離されて以来 ^{1, 2)}、ソゾ属からは、現在までに 600 を超える多様なハロゲン化合物 (主に臭素付加化合物) が単離・報告されている ³⁾。これらソゾ由来含臭素化合物の生合成における鍵反応は、環形成を伴った臭素付加反応と考えられている。

村井らは、同過程の触媒酵素の候補として、ブロモペルオキシダーゼ (BPO) をウラソゾから部分精製し ⁴⁾、1 の推定生合成前駆体 laurediol (2) ⁵⁾ を用いた臭素付加・環形成実験に供した。その結果、部分精製 BPO は、2 から deacetyllaurencin (3) への臭素付加・環形成を触媒することが示された (Scheme 1) ⁴⁾。酵素生成物である 3 は、1 の生合成最終前駆体であることから、1 の臭素付加・環形成過程は、BPO により触媒されることが示唆された。一方で、ウラソゾ BPO の構造および生化学的知見は、現在に至るまで明らかにされていない。

他の紅藻 Corallina 属などでは、BPOの結晶構造が解明されており、活性中心にバナジン酸 (VO₄^3-) を要求するバナジウム依存型 BPO (VBPO) であると報告されている ⁶⁾。そこで、本研究では、ソゾ由来の臭素付加酵素の同定のため、ウラソゾより VBPO 遺伝子クローニングを行った。また、ウラソゾ VBPO組み換えタンパク質を調製し、生化学的特性の評価とソゾ由来臭素化合物の推定前駆体を用いた in vitro 臭素付加反応を行い、生合成における役割を評価した。



Scheme 1. In vitro enzymatic bromination of laurediol using partially purified BPO from L. nipponica ⁴⁾.

ウラソゾ由来 VBPO の cDNA クローニングと組み換えタンパク質の調製

RACE PCR 法によって、ウラソゾ VBPO cDNA クローニングを行った結果、二種類のウラソゾVBPO 全長配列 (LnVBPO1およびLnVBPO2, 95% identity) を取得した。両遺伝子を、それぞれ大腸菌発現系 BL21 (DE3) pLysS に導入後、可溶画分を抽出し、硫安沈殿と DE52 陰イオン交換クロマトグラフィによって、LnVBPO1 および LnVBPO2組み換えタンパク質を精製した。得られたタンパク質をSDS-PAGE に供したところ、いずれも 77 kDa の位置に単一のバンドとして泳動された。また、両組み換えタンパク質は、ゲルろ過において最大で750 kDa 程度であり、10 量体を形成することが推定された。VBPO においては、紅藻 Corallina 由来 VBPO も 12 量体を形成することが知られている ^7,8) 。

次に、藻体由来の BPO と LnVBPOs 組み換えタンパク質との同一性を検証するため、同様な精製方法を用いて、ウラソゾ藻体から BPO の精製を試みた。藻体由来 BPO は、色素成分との分離が困難であり、部分精製に留まった。組み換え LnVBPOs と部分精製 BPO をSDS-PAGE に供したところ、ともに 75 kD

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オマエザレンの全合成と絶対立体化学の決定
梅澤 大樹, 山崎 翔平, 小栗 祐子, 松浦 裕志, 鈴木 将洋, 沖野 龍文, 松田 冬彦
天然有機化合物討論会講演要旨集, 55, Oral24, 天然有機化合物討論会実行委員会, 2013年
日本語, Omaezallene (1)は、2007年に静岡県御前崎で採取されたソゾ属から単離された天然有機化合物であり、タテジマフジツボのキプリス幼生の付着を低濃度(EC₅₀ = 0.22 mg / mL)で阻害することが明らかにされている。船底などにフジツボなどが付着すると航行速度の低下を引き起こし、燃費が劇的に悪くなる。付着阻害物質として、これまでは有機スズ化合物が世界中で広く使用されてきたが、貝類の成長阻害を引き起こしたり、メスの巻貝をオス化させるなど、その毒性のため2008年に国際海事機関 (IMO)によってその使用が禁止された。そのため、毒性の少ない天然有機化合物由来の付着阻害物質の創製が求められており、1はそのリード化合物として期待される。1の立体化学は以下のように推定した。ブロモアレンを除く部分の相対立体配置は天然の1をアセトニド化し2環性化合物2に導いた後にNOE測定し、その相関から図のように推定したが、C9位の相対立体化学については、NOEだけでは確定できなかった。ブロモアレンの絶対立体化学は、1の比旋光度が-127で負の値であったことから、Lowe則¹⁾によりRであると推定した。しかしながら、アレンに対するTHF環部の相対立体化学およびアレン以外の絶対立体化学は類似化合物であるAplysiallene²⁾との比較による推定にとどまった。今回、Omaezalleneの全合成を達成するとともに、その絶対立体化学を確定することができた。本発表ではその詳細について発表する。

合成計画

構造決定を行うためには、1つの中間体から、予想される2種の立体異性体(Rのブロモアレンに対する、THF環部の両エナンチオマー)に柔軟にアプローチできるルートが理想である。このことを念頭に置いて、Scheme 1に示すOmaezalleneの合成計画を立案した。D-glucoseから誘導できる既知のアルデヒド3を出発化合物に用いて、Wittig反応でE-オレフィンを構築後、アセタールを脱保護して得られるヘミアセタールに対して、アセチリドを付加してトリオール4を合成する。4にNBSなどを作用させるブロモエーテル化によって2連続不斉中心を一挙に構築し、テトラヒドロフラン 5とする。次に、Aplysialleneをはじめとしたブロモアレン類の合成の際にも用いられた既知の方法を適用して、立体特異的に進行するブロモアレン化、続く保護基の変換を経てアルデヒド6へと導く。最後に、アルデヒドを足掛かりとしたC9位水酸基の導入を経て、ブロモジエンを構築後、脱保護によって1を合成することにした。また、THF環部のもう一方のエナンチオマーの合成には3の隠れた対称性を利用することにした。すなわち、3にアセチリドを付加して7とし、アセトニドの脱保護により得られるアセタールにWittig試薬を作用させると、ent-4が合成できると考えた。

Scheme 1. Synthetic Plan toward Omaezallene

アルデヒド6の合成

D-glucoseから5段階で合成した3を用いて、E-選択的Wittig反応を試みた。トリフェニルホスフィン由来の試薬ではEZ選択性は最高で2:1にとどまったが、Martinらが報告したトリブチルホスフィンから合成したWittig試薬³では10:1にまで選択性が向上した。エステルを還元し、生じた水酸基を保護し

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Confirmation of the Configuration of 10-Isothiocyanato-4-cadinene Diastereomers through Synthesis
Keisuke Nishikawa, Taiki Umezawa, Mary J. Garson, Fuyuhiko Matsuda
JOURNAL OF NATURAL PRODUCTS, 75, 12, 2232, 2235, AMER CHEMICAL SOC, 2012年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

P-11 アルデヒド、酸フッ化物、トリメチルシリルメチルポスホネートの3成分カップリング反応(ポスター発表の部)
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
日本語, 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)

Thrombin Inhibitors from the Freshwater Cyanobacterium Anabaena compacta
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, AMER CHEMICAL SOC, 2012年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Novel One-pot Three-component Coupling Reaction with Trimethylsilylmethylphosphonate, Acyl Fluoride, and Aldehyde through the Horner-Wadsworth-Emmons Reaction
Taiki Umezawa, Tomoya Seino, Fuyuhiko Matsuda
ORGANIC LETTERS, 14, 16, 4206, 4209, AMER CHEMICAL SOC, 2012年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

Synthesis and Biological Activity of Kalkitoxin and its Analogues
Taiki Umezawa, Manabu Sueda, Takao Kamura, Teppei Kawahara, Xuerong Han, Tatsufumi Okino, Fuyuhiko Matsuda
JOURNAL OF ORGANIC CHEMISTRY, 77, 1, 357, 370, AMER CHEMICAL SOC, 2012年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

1 光学活性 Danicalipin Aの全合成(口頭発表の部)
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
日本語, 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.

P-31 Kalkitoxin及びその類縁体の合成と生物活性(ポスター発表の部)
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
日本語, 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.

P-80 Isocyanocadineneの全合成(ポスター発表の部)
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
日本語, 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.

1,2-ジブロモアルケンからのアルキン合成
奥村日向, 諸角達也, 梅澤大樹, 化学系学協会北海道支部冬季研究発表会(Web), 2024, 2024年

¹³C標識メタクロレインを用いたH₃PMo₁₂O₄₀上でのメタクロレイン酸化反応における副反応経路の解析
菅野充, 平田純, 梅澤大樹, 二宮航, 神谷裕一, Journal of the Japan Petroleum Institute (Web), 66, 4, 2023年

海洋付着生物に対する付着阻害有機化合物の創製の試み 付着阻害ユニットを組み込んだ効率的な化合物の合成
梅澤大樹, 化学と生物, 61, 7, 2023年

¹³C同位体標識基質を用いたH₃PMo₁₂O₄₀上でのメタクロレイン酸化反応機構の解析
菅野充, 平田純, 梅澤大樹, 二宮航, 神谷裕一, 触媒討論会討論会A予稿集(CD-ROM), 130th, 2022年

褐藻類の性フェロモン,ムルチフィデンの合成研究
原美咲, 松田冬彦, 梅澤大樹, 天然有機化合物討論会講演要旨集(Web), 62nd, 2020年

Dolastatin16誘導体の合成研究
早川嘉樹, 中村謙介, CASALME Loida O., 梅澤大樹, 松田冬彦, 天然有機化合物討論会講演要旨集(Web), 60th, 2018年

有機合成から着生問題へのアプローチ:着生機構解明のためのプローブ化を志向した着生阻害天然物の合成研究
梅澤大樹, Sessile Organisms, 35, 1, 2018年

着生阻害活性天然有機化合物と誘導体の合成研究
梅澤大樹, 松田冬彦, Sessile Organisms, 35, 2, 2018年

マリンバイオマス由来付着阻害剤の構造―活性相関研究
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
日本語

グルコサミン由来の付着阻害剤の合成と付着阻害活性
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

Synthetic study on dolastatin 16: concise and scalable synthesis of two unusual amino acid units
Taiki Umezawa, Akinori Sato, Yasuto Ameda, Loida O. Casalme, Fuyuhiko Matsuda, TETRAHEDRON LETTERS, 56, 1, 168, 171, 2015年01月
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., PERGAMON-ELSEVIER SCIENCE LTD, 英語

Recent progress toward synthesis of chlorosulfolipids: total synthesis and methodology
Taiki Umezawa, Fuyuhiko Matsuda, TETRAHEDRON LETTERS, 55, 19, 3003, 3012, 2014年05月
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., PERGAMON-ELSEVIER SCIENCE LTD, 英語

紅藻ウラソゾLaurencia nipponica由来バナジウム依存型ブロモペルオキシダーゼの性状解析
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
日本語

Danicalipin A誘導体の合成研究
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
日本語

Dolastatin16の全合成研究
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
日本語

効率的ビニグロールの合成研究
梅澤大樹, 上原記念生命科学財団研究報告集(CD-ROM), 27, ROMBUNNO.11, 4, 2013年12月10日
上原記念生命科学財団, 日本語

紅藻ウラソゾLaurencia nipponica由来バナジウム依存型ブロモペルオキシダーゼの性状解析
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
日本語

Mytilipin Cの全合成研究
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
日本語

アルデヒド,酸フッ化物,トリメチルシリルメチルホスホネートの3成分カップリング反応
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
日本語

クロロスルフォリピッド類の立体選択的全合成
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
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., SOC SYNTHETIC ORGANIC CHEM JPN, 日本語, 書評論文,書評,文献紹介等

Stereoselective total syntheses of chlorosulfolipids
Taiki Umezawa, Fuyuhiko Matsuda, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 69, 10, 1122, 1133, 2011年10月
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., SOC SYNTHETIC ORGANIC CHEM JPN, 日本語, 書評論文,書評,文献紹介等

オマエザレンの全合成
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
日本語

支部発 話題欄 1 天然有機化合物の化学 含ハロゲン化合物の全合成
梅澤大樹, 化学と工業, 64, 9, 688, 689, 2011年09月01日
日本語

Total Synthesis of 10-Isocyano-4-cadinene and Its Stereoisomers and Evaluations of Antifouling Activities
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, ［国際誌］
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., AMER CHEMICAL SOC, 英語

Asymmetric Total Synthesis of Danicalipin A and Evaluation of Biological Activity
Taiki Umezawa, Masayuki Shibata, Kensuke Kaneko, Tatsufumi Okino, Fuyuhiko Matsuda, ORGANIC LETTERS, 13, 5, 904, 907, 2011年03月, ［国際誌］
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., AMER CHEMICAL SOC, 英語

Synthesis of C-13-Labeled 5,6,11-Trideoxytetrodotoxin
Taiki Umezawa, Tetsuro Shinada, Yasufumi Ohfune, CHEMISTRY LETTERS, 39, 12, 1281, 1282, 2010年12月
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, CHEMICAL SOC JAPAN, 英語

Mild and Catalytic Transesterification Reaction Using K2HPO4 for the Synthesis of Methyl Esters
Tetsuro Shinada, Makoto Hamada, Kota Miyoshi, Masato Higashino, Taiki Umezawa, Yasufumi Ohfune, SYNLETT, 14, 2141, 2145, 2010年09月
K2HPO4 is an efficient catalyst for the transesterification reaction to produce methyl esters. Various functional groups are compatible under the mild reaction conditions., GEORG THIEME VERLAG KG, 英語

Synthesis of the QRSTU Domain of Maitotoxin and Its 85-epi- and 86-epi-Diastereoisomers
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
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., AMER CHEMICAL SOC, 英語

Isocyanocadinene及びその立体異性体の合成とそれらの着生阻害活性の評価
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
日本語

Total Synthesis of 10-Isocyano-4-cadinene and Determination of Its Absolute Configuration
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
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., AMER CHEMICAL SOC, 英語

テルペン類の全合成 : 骨格形成法の新展開
松田 冬彦, 梅澤 大樹, ファルマシア, 44, 10, 959, 964, 2008年10月01日
公益社団法人日本薬学会, 日本語

Chemical synthesis of the GHIJKLMNO ring system of maitotoxin
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
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)., AMER CHEMICAL SOC, 英語

Total synthesis of (-)-5,6,11-trideoxytetrodotoxin and its 4-epimer
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
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., AMER CHEMICAL SOC, 英語

P-107 TOTAL SYNTHESIS OF 5,6,11-TRIDEOXYTETRODOTOXIN
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
天然有機化合物討論会, 英語

P-216 SYNTHESIS OF STELLETTADINE A BY NOVEL METHOD FOR THE SYNTHESIS OF N-ACYL-N'-SUBSTITUTED GUANIDINES
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
天然有機化合物討論会, 英語

On the stereoselectivity of asymmetric strecker synthesis in a cyclohexane system: Synthesis of optically active cis- and trans-1-amino-2-hydroxycyclohexane-1-carboxylic acids
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
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., CHEMICAL SOC JAPAN, 英語

On the stereoselectivity of asymmetric strecker synthesis in a cyclohexane system: Synthesis of optically active cis- and trans-1-amino-2-hydroxycyclohexane-1-carboxylic acids
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
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., CHEMICAL SOC JAPAN, 英語

A New Entry for the Synthesis of N-Acyl-N’-substituted Guanidines
SHINADA Tetsuro, UMEZAWA Taiki, ANDO Tsuyoshi, KOZUMA Hayato, OHFUNE Yasufumi, Tetraheron Letters, 47, 12, 1945, 1947, 2006年03月
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., PERGAMON-ELSEVIER SCIENCE LTD, 英語

14 5,,6,11-トリデオキシテトロドトキシンの全合成(口頭発表の部)
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
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., 天然有機化合物討論会実行委員会, 日本語

2021年04月 - 現在
日本農芸化学会　　　　　　　　　　　　　　　

若手研究者のための有機合成セミナー　　　　　　　　　　　　　　　
2008年

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　　　　　　　　　　　　　　　
基盤研究（B)
2018年04月 - 2022年03月
梅澤 大樹
科研費, 研究代表者, 競争的資金

分解反応を利用した官能基間距離が精密に制御された固体表面反応場の構築
科学研究費助成事業
2019年06月28日 - 2021年03月31日
神谷 裕一, 大友 亮一, 梅澤 大樹
シリカの表面に固定したアミド化合物を加水分解することで、酸点（カルボキシ基）と塩基点（アミノ基）が隣接した位置に必ず配置される酸ー塩基ペアサイトを持つ固体触媒を合成した。この触媒は4-ニトロベンズアルデヒドとアセトンとの交差アルドール縮合に高い触媒活性を示した。一方、その構造の内部に３つの炭素原子からなるメチレン基をリンカーとするジアミド化合物を用いて、酸点と塩基点がリンカー相当の距離だけ離れた酸ー塩基ペアサイトを持つ触媒を合成した。この触媒は隣接した酸ー塩基ペアサイトを持つ触媒よりも低い活性しか示さず、酸点と塩基点の間の距離が重要な支配因子であることが確かめられた。
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 19K22074

含ハロゲン船底防汚物質のケミカルバイオロジー
科学研究費助成事業
2016年04月01日 - 2020年03月31日
沖野 龍文, 野方 靖行, 梅澤 大樹, 森本 善樹
紅藻マギレソゾのバナジウム依存型ブロモペルオキシダーゼのスクワレンテトラエポキシドについて、反応条件を最適化することに成功し、MSレベルで産物を同定した。海洋藍藻から、塩素を含む長鎖アシルアミドであるコロンバマイド、含塩素ペプチドのリングビアベリンを単離・構造決定し、一部は全合成にも成功した。また、臭素を含むオマエザレンの誘導体を合成し、その付着阻害活性を評価した。
日本学術振興会, 基盤研究(B), 北海道大学, 16H04975

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　　　　　　　　　　　　　　　
環境総合研究推進費
2016年04月 - 2018年03月
梅澤 大樹
環境省, 研究代表者, 競争的資金

船底防汚塗料候補物質含ハロゲン化合物の酵素反応による合成
科学研究費助成事業
2012年04月01日 - 2016年03月31日
沖野 龍文, 松田 冬彦, 梅澤 大樹, 野方 靖行, 鷲尾 健司
含ハロゲン化合物であるローレンシンを生産するウラソゾから、その生合成酵素の一つとして環化と臭素化を触媒するバナジウム依存型ブロモペルオキシダーゼのクローニングに成功し、組換え酵素を用いてその臭素化活性を明らかにした。含ハロゲンセスキテルペノイドであるローリンテロールを生産するミツデソゾから、バナジウム依存型ブロモペルオキシダーゼのクローニングに成功し、その性状を明らかにした。さらに、含ハロゲントリテルペノイドを生産するマギレソゾから、同酵素のクローニングに成功し、その性状を明らかにした。ブロモアレンを有するC15化合物であるオマエザレンの構造を報告すると共に、その全合成に成功した。
日本学術振興会, 基盤研究(B), 北海道大学, 24380112

付着阻害活性天然物のメカニズム解明を目指した蛍光プローブの合成研究
科学研究費補助金(若手研究(B))
2015年 - 2016年
梅澤 大樹
本研究では、付着生物に対する付着阻害活性天然有機化合物をリードとし、蛍光プローブ合成を目的とする。阻害剤のリード化合物として、強い付着阻害活性と低毒性を併せ持つOmaezallene（含臭素化合物）とDolastatin 16（環状ペプチド）に着目した。これらの付着阻害メカニズムを解明をすることで、理想的な化合物開発の糸口となる。
Omaezalleneでは、合成経路を応用することで、種々の誘導体を合成し、構造活性相関研究を進蛍光標識体を合成できた。Dolastatin 16では、合成経路を確立するとともに、強力な付着阻害活性を持つことが明らかにした。
文部科学省, 若手研究(B), 北海道大学, 研究代表者, 競争的資金, 15K16551

毒性発現機構の解明を指向したクロロスルフォリピッドの合成研究
科学研究費補助金(若手研究(B))
2011年 - 2012年
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。
文部科学省, 若手研究(B), 北海道大学, 研究代表者, 競争的資金, 23710245

海洋付着生物に対する付着阻害作用を有するオリゴペプチド　　　　　　　　　　　　　　　
特許権
特願P2023-075-JP01, 2023年10月06日

学士課程, 理学部

修士課程, 環境科学院

博士課程, 環境科学院