博士（薬科学）, 北海道大学, Mar. 2018

medicinal chemistry

natural product

organic chemistry

Nanotechnology/Materials, Structural organic chemistry and physical organic chemistry

Life Science, Pharmaceutical chemistry and drug development sciences

Life Science, Pharmaceutical chemistry and drug development sciences, synthetic organic chemistry

Bachelor's degree program, School of Pharmaceutical Sciences and Pharmacy

Master's degree program, Graduate School of Life Science

Doctoral (PhD) degree program, Graduate School of Life Science

Oct. 2017, 博士課程教育リーディングプログラムフォーラム2017, Academia Future Leader Award
勝山 彬

Sep. 2017, 第59回天然有機化合物討論会, 奨励賞
勝山 彬

Apr. 2015, 第27回 万有札幌シンポジウム, Best Poster
KATSUYAMA AKIRA

May 2014, 日本薬学会北海道支部, 141回日本薬学会北海道支部例会学生優秀発表賞
勝山 彬;松田彰;市川聡

Sparfloxacin reveals a host–virus dual-target antiviral scaffold against respiratory syncytial virus
Yuka Takumi-Tanimukai; Soh Yamamoto; Yurie Yoshida; Tatsuki Takahashi; Akira Takasawa; Akira Katsuyama; Takumi Nishimaki; Haruka Maeda; Katsumi Mizuta; Masashi Idogawa; Yukari Mitsuhashi; Yume Takayanagi; Sithumini M. W. Lokupathirage; Keitaro Yoshida; Keisuke Yamamoto; Takuya Kakuki; Sumito Jitsukawa; Toyotaka Sato; Hirofumi Sawa; Yasuko Orba; Akihiko Sato; Takashi Kojima; Wataru Kamitani; Satoshi Ichikawa; Tetsuya Nosaka; Kenichi Takano; Shin-ichi Yokota; Noriko Ogasawara
Communications Biology, 08 Aug. 2026
Scientific journal

Asymmetric Total Synthesis of (+)-Acaulone B
Sho Fujii; Jun Hirabayashi; Akira Katsuyama; Satoshi Ichikawa; Fumika Yakushiji
The Journal of Organic Chemistry, 91, 26, 9238, 9242, American Chemical Society (ACS), 23 Jun. 2026
Scientific journal

Total Synthesis, Antibacterial Activity, and Structural Analysis of Atratumycin and Its Analogues
Yuya Sawayama; Rintaro Kaguchi; Motoko Shinohara; Yusuke Minato; Satoshi Ichikawa; Akira Katsuyama
Organic Letters, 28, 13, 4032, 4037, American Chemical Society (ACS), 17 Mar. 2026
Scientific journal

Optimization of galectin-3 binding agents by in situ multiple compound synthesis and native mass spectrometry
Kazuki Hoshi; Tsuyoshi Konuma; Rina Taguchi; Satoko Akashi; Yoshiya Katahira; Akira Katsuyama; Satoshi Ichikawa
Scientific Reports, 16, 1, 8453, Springer Science and Business Media LLC, 12 Feb. 2026, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Ozonated olive oil inhibits melanoma proliferation by inducing ferroptosis
Seong-Jin An; Jun-Ichi Kashiwakura; Akira Katsuyama; Sumihito Togi; Yuichi Kitai; Ryuta Muromoto; Toshiaki Miura; Satoshi Ichikawa; Tadashi Matsuda
Biochemistry and Biophysics Reports, 44, 102267, 102267, Elsevier BV, Dec. 2025
Scientific journal

Retrosynthetic Analysis-Aware Fragment Linking for Structure-Guided Ligand Extension
Akira Katsuyama; Yasuaki Tokodai; Kazuki Hoshi; Satoshi Ichikawa
ChemRxiv, 20 Nov. 2025, [Lead author, Corresponding author]

Non-ribosomal peptide cyclase-directed chemoenzymatic synthesis of lariat lipopeptides
Masakazu Kobayashi; Kenichi Matsuda; Yuito Yamada; Rintaro Ichihara; Naho Onozawa; Hanako Fukano; Yoshihiko Hoshino; Aki Hirabayashi; Masato Suzuki; Akira Katsuyama; Satoshi Ichikawa; Toshiyuki Wakimoto
Nature Chemistry, 18, 1, 180, 188, Springer Science and Business Media LLC, 04 Nov. 2025
Scientific journal

Structure–Activity Relationship of Pseudouridimycin Focusing on the Improvement of Chemical Stability
Ryotaro Okawa; Irina Artsimovitch; Akira Katsuyama; Toyotaka Sato; Courtney C. Aldrich; Satoshi Ichikawa
Journal of Medicinal Chemistry, 14 Aug. 2025
Scientific journal

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality
Ryota Kimura; Satoshi Ichikawa; Akira Katsuyama
Beilstein Journal of Organic Chemistry, 04 Aug. 2025
Scientific journal

Development of small molecule–drug conjugates based on derivatives of natural proteasome inhibitors that exhibit selectivity for PSMA-expressing cancer cells
Takahiro Obara; Nanami Kawano; Kengo Tatsumi; Akira Katsuyama; Kohei Nakajima; Mikako Ogawa; Satoshi Ichikawa
Bioorganic & Medicinal Chemistry, 108, 117773, 117773, Elsevier BV, Jun. 2024, [Peer-reviewed]
Scientific journal

Modulation of proteasome subunit selectivity of syringolins
Kengo Tatsumi; Shun Kitahata; Yuya Komatani; Akira Katsuyama; Fumika Yakushiji; Satoshi Ichikawa
Bioorganic & Medicinal Chemistry, 106, 117733, 117733, Elsevier BV, May 2024, [Peer-reviewed]
Scientific journal

Synthesis and biological evaluation of echinomycin analogues as potential colon cancer agent
Keita Kojima; Hiroaki Konishi; Kyoka Momosaki; Yuya Komatani; Akira Katsuyama; Koji Nakagawa; Kayoko Kanamitsu; Fumika Yakushiji; Mikihiro Fujiya; Satoshi Ichikawa
Scientific Reports, 14, 1, Springer Science and Business Media LLC, 01 Apr. 2024, [Peer-reviewed]
English, Scientific journal, Abstract

Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death, thus a novel chemotherapeutic agent for colon cancer therapy is needed. In this study, analogues of echinomycin, a cyclic peptide natural product with potent toxicity to several human cancer cell lines, were synthesized, and their biological activities against human colon cancer cells were investigated. Analogue 3 as well as 1 inhibit HIF-1α-mediated transcription. Notably, transcriptome analysis indicated that the cell cycle and its regulation were involved in the effects on cells treated with 3. Analogue 3 exhibited superior in vivo efficacy to echinomycin without significant toxicity in mouse xenograft model. The low dose of 3 needed to be efficacious in vivo is also noteworthy and our data suggest that 3 is an attractive and potentially novel agent for the treatment of colon cancer.

Photoinduced dual bond rotation of a nitrogen-containing system realized by chalcogen substitution
Shotaro Nagami; Rintaro Kaguchi; Taichi Akahane; Yu Harabuchi; Tohru Taniguchi; Kenji Monde; Satoshi Maeda; Satoshi Ichikawa; Akira Katsuyama
Nature Chemistry, Springer Science and Business Media LLC, 28 Feb. 2024, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Concise Synthesis of 11-Noriridoids via Pauson-Khand Reaction.
Ryuji Kouda; Kazuki Yamamoto; Akira Katsuyama; Satoshi Ichikawa; Fumika Yakushiji
Chemical & pharmaceutical bulletin, 72, 6, 547, 558, 2024, [Domestic magazines]
English, Scientific journal, Iridoids, which are a class of monoterpenoids, are attractive synthetic targets due to their diversely substituted cis-fused cyclopenta[c]pyran skeletons. Additionally, various biological activities of iridoids raise the value of synthetic studies on this class of compounds. Here, our synthetic efforts toward 11-noriridoids; (±)-umbellatolide B (6), (±)-10-O-benzoylglobularigenin (9) and 1-O-pentenylaucubigenin (34) are described. For the efficient synthesis of target compounds, common synthetic intermediates (tricyclic enones 17 and 26) were prepared by the Pauson-Khand reaction. The cleavage of the acetal bond on the tricyclic enones and 1,2-reduction introduced the two hydroxy groups on the cyclopentane ring of the core scaffold. Furthermore, the C3-C4 olefin part was constructed by the syn-elimination of a thiocarbonate moiety to obtain 34. The developed synthetic routes for 6, 9, and 34 will be useful for the preparation of iridoid analogs that have a polyfunctionalized core skeleton.

Determining the structure of protein-bound ceramides, essential lipids for skin barrier function.
Yusuke Ohno; Tetsuya Nakamura; Takafumi Iwasaki; Akira Katsuyama; Satoshi Ichikawa; Akio Kihara
iScience, 26, 11, 108248, 108248, 17 Nov. 2023, [International Magazine]
English, Scientific journal, Protein-bound ceramides, specialized ceramides covalently bound to corneocyte surface proteins, are essential for skin permeability barrier function. However, their exact structure and target amino acid residues are unknown. Here, we found that epoxy-enone (EE) ceramides, precursors of protein-bound ceramides, as well as their synthetic analog, formed stable conjugates only with Cys among nucleophilic amino acids. NMR spectroscopy revealed that the β-carbon of the enone was attached by the thiol group of Cys via a Michael addition reaction. We confirmed the presence of Cys-bound EE ceramides in mouse epidermis by mass spectrometry analysis of protease-digested epidermis samples. EE ceramides were reversibly released from protein-bound ceramides via sulfoxide elimination. We found that protein-bound ceramides with reversible release properties accounted for approximately 60% of total protein-bound ceramides, indicating that Cys-bound EE ceramides are the predominant protein-bound ceramides. Our findings provide clues to the molecular mechanism of skin barrier formation by protein-bound ceramides.

Solid-Phase Synthesis of Nannocystin Ax and Its Analogues.
Daiki Miyakita; Kohei Kawanishi; Akira Katsuyama; Kazuki Yamamoto; Fumika Yakushiji; Satoshi Ichikawa
The Journal of organic chemistry, 88, 15, 11367, 11371, 04 Aug. 2023, [International Magazine]
English, Scientific journal, Solid-phase total synthesis of nannocystin Ax (1) was disclosed. A coupling reaction between a peptide and a polyketide moiety was conducted on a solid support, and macrocyclization was achieved by Mitsunobu cyclization. The established synthetic route was efficient to prepare its analogues, which contain different types of peptide moieties.

Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry
Rintaro Kaguchi; Akira Katsuyama; Toyotaka Sato; Satoshi Takahashi; Motohiro Horiuchi; Shin-ichi Yokota; Satoshi Ichikawa
Journal of the American Chemical Society, 145, 6, 3665, 3681, American Chemical Society (ACS), 28 Jan. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Peptides can be converted to highly active compounds by introducing appropriate substituents on the suitable amino acid residue. Although modifiable residues in peptides can be systematically identified by peptide scanning methodologies, there is no practical method for optimization at the "scanned" position. With the purpose of using derivatives not only for scanning but also as a starting point for further chemical functionalization, we herein report the "scanning and direct derivatization" strategy through chemoselective acylation of embedded threonine residues by a serine/threonine ligation (STL) with the help of in situ screening chemistry. We have applied this strategy to the optimization of the polymyxin antibiotics, which were selected as a model system to highlight the power of the rapid derivatization of active scanning derivatives. Using this approach, we explored the structure-activity relationships of the polymyxins and successfully prepared derivatives with activity against polymyxin-resistant bacteria and those with Pseudomonas aeruginosa selective antibacterial activity. This strategy opens up efficient structural exploration and further optimization of peptide sequences.

Solid-Phase Total Synthesis of Sandramycin and Its Analogues
Yuya Komatani; Kyoka Momosaki; Akira Katsuyama; Kazuki Yamamoto; Rintaro Kaguchi; Satoshi Ichikawa
Organic Letters, 25, 3, 543, 548, American Chemical Society (ACS), 27 Jan. 2023, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY.
Takeshi Nakaya; Miyuki Yabe; Ellene H Mashalidis; Toyotaka Sato; Kazuki Yamamoto; Yuta Hikiji; Akira Katsuyama; Motoko Shinohara; Yusuke Minato; Satoshi Takahashi; Motohiro Horiuchi; Shin-Ichi Yokota; Seok-Yong Lee; Satoshi Ichikawa
Nature communications, 13, 1, 7575, 7575, 20 Dec. 2022, [International Magazine]
English, Scientific journal, The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring macrocyclic nucleoside inhibitors of MraY and are considered a promising target in antibacterial discovery. However, developing sphaerimicins as antibacterials has been challenging due to their complex macrocyclic structures. In this study, we construct their characteristic macrocyclic skeleton via two key reactions. Having then determined the structure of a sphaerimicin analogue bound to MraY, we use a structure-guided approach to design simplified sphaerimicin analogues. These analogues retain potency against MraY and exhibit potent antibacterial activity against Gram-positive bacteria, including clinically isolated drug resistant strains of S. aureus and E. faecium. Our study combines synthetic chemistry, structural biology, and microbiology to provide a platform for the development of MraY inhibitors as antibacterials against drug-resistant bacteria.

Solid-Phase Total Synthesis of Plusbacin A3.
Kazuki Takashina; Akira Katsuyama; Rintaro Kaguchi; Kazuki Yamamoto; Toyotaka Sato; Satoshi Takahashi; Motohiro Horiuchi; Shin-Ichi Yokota; Satoshi Ichikawa
Organic letters, 24, 11, 2253, 2257, 25 Mar. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, The total synthesis of the depsipeptide natural product plusbacin A3 (1) utilizing solid-phase peptide synthesis (SPPS) was disclosed. A 3-hydroxy-proline derivative compatible with Fmoc SPPS was prepared by a diastereoselective Joullié-Ugi three-component reaction (JU-3CR)/hydrolysis sequence. After peptide elongation on the solid support, cleavage of the peptide from the resin, followed by macrolactamization and global deprotection, gave plusbacin A3 (1).

Solid-phase synthesis of fluorescent analogues of Park’s nucleotide, lipid I and lipid II
Akira Katsuyama; Fumika Yakushiji; Satoshi Ichikawa
Tetrahedron Letters, 153101, 153101, Elsevier BV, Jun. 2021, [Lead author]
Scientific journal

Structure, solubility, and permeability relationships in a diverse middle molecule library
Hiroyuki Miyachi; Kayoko Kanamitsu; Mayumi Ishii; Eri Watanabe; Akira Katsuyama; Satoko Otsuguro; Fumika Yakushiji; Mizuki Watanabe; Kouhei Matsui; Yukina Sato; Satoshi Shuto; Takashi Tadokoro; Shunsuke Kita; Takanori Matsumaru; Akira Matsuda; Tomoyasu Hirose; Masato Iwatsuki; Yasuteru Shigeta; Tetsuo Nagano; Hirotatsu Kojima; Satoshi Ichikawa; Toshiaki Sunazuka; Katsumi Maenaka
Bioorganic & Medicinal Chemistry Letters, 37, 127847, 127847, Elsevier BV, Feb. 2021, [Peer-reviewed]
Scientific journal

Elucidating the Structural Requirement of Uridylpeptide Antibiotics for Antibacterial Activity
Yuma Terasawa; Chisato Sataka; Toyotaka Sato; Kazuki Yamamoto; Yukari Fukushima; Chie Nakajima; Yasuhiko Suzuki; Akira Katsuyama; Takanori Matsumaru; Fumika Yakushiji; Shin-ichi Yokota; Satoshi Ichikawa
Journal of Medicinal Chemistry, 63, 17, 9803, 9827, American Chemical Society (ACS), 10 Sep. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The synthesis and biological evaluation of analogues of uridylpeptide antibiotics were described, and the molecular interaction between the 3'-hydroxy analogue of mureidomycin A (3'-hydroxymureidomycin A) and its target enzyme, phospho-MurNAc-pentapeptide transferase (MraY), was analyzed in detail. The structure-activity relationship (SAR) involving MraY inhibition suggests that the side chain at the urea-dipeptide moiety does not affect the MraY inhibition. However, the anti-Pseudomonas aeruginosa activity is in great contrast and the urea-dipeptide motif is a key contributor. It is also suggested that the nucleoside peptide permease NppA1A2BCD is responsible for the transport of 3'-hydroxymureidomycin A into the cytoplasm. A systematic SAR analysis of the urea-dipeptide moiety of 3'-hydroxymureidomycin A was further conducted and the antibacterial activity was determined. This study provides a guide for the rational design of analogues based on uridylpeptide antibiotics.

Total Synthesis of Acaulide and Acaulone A
Jun Hirabayashi; Fumika Yakushiji; Akira Katsuyama; Satoshi Ichikawa
Organic Letters, 22, 14, 5545, 5549, American Chemical Society (ACS), 17 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Acaulide and acaulone A, which contain 14-membered macrodiolides, were isolated from a culture of Acaulium sp. H-JQSF. The antiosteoporosis activity of acaulide is expected to contribute to drug discovery research for an aging society. We herein report the first total synthesis of acaulide, acaulone A, and 10-keto-acaudiol A. Acaulide and acaulone A were synthesized via the late stage Michael addition to the 14-membered macrodiolide, which was inspired by plausible biosynthetic pathways. This approach succeeded in the construction of the acaulide skeleton, which revealed the specific conformation of the 14-membered macrodiolide for late stage functionalization.

Total Synthesis of Echinomycin and Its Analogues
Keita Kojima; Fumika Yakushiji; Akira Katsuyama; Satoshi Ichikawa
Organic Letters, 22, 11, 4217, 4221, American Chemical Society (ACS), 05 Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The first total synthesis of echinomycin (1) was accomplished by featuring the late-stage construction of the thioacetal moiety via Pummerer rearrangement and simultaneous cyclization, as well as two-directional elongation of the peptide chains to construct a C2-symmetrical bicyclic octadecadepsipeptide bridged with a sulfide linkage. This strategy can be applicable to a variety of echinomycin analogues.

A Synthesis Strategy for the Production of a Macrolactone of Gulmirecin A via a Ni(0)-Mediated Reductive Cyclization Reaction
Shun Kitahata; Akira Katsuyama; Satoshi Ichikawa
Organic Letters, 22, 7, 2697, 2701, American Chemical Society (ACS), 03 Apr. 2020, [International Magazine]
English, Scientific journal, A synthesis strategy for the production of a key synthetic intermediate of gulmirecin A was described. The key reaction in the preparation of the 12-membered macrolactone is the Ni(0)-mediated reductive cyclization reaction of ynal using an N-heterocyclic carbene ligand and silane reductant. In addition, the α-selective glycosylation reaction of the macrolactone was performed to demonstrate the synthesis of gulmirecin and disciformycin precursors.

Development of cyclic peptide derivatives from the N-terminal region of LANA for targeting the nucleosome acidic patch.
Fumika Yakushiji; Aoi Ishikawa; Akira Katsuyama; Satoshi Ichikawa
Bioorganic & medicinal chemistry letters, 30, 2, 126839, 126839, 15 Jan. 2020, [International Magazine]
English, Scientific journal, Kaposi's sarcoma-associated herpesvirus (KSHV) is known to be a carcinogenic agent that causes AIDS-associated Kaposi's sarcoma (KS). When KSHV infects host's cells, one of the virus's proteins, latency-associated nuclear antigen 1 (LANA), binds to the host's nucleosomes to retain episomes and create latency circumstances. Although the infectious mechanism of KSHV is partly elucidated, the development of drug candidates for targeting KS is ongoing. In this study, we developed cyclic peptides corresponding to an N-terminal LANA sequence that disrupt the LANA-nucleosome interaction. The cyclic peptides showed a different secondary structure compared to their corresponding linear peptide derivatives, which suggests that our cyclization strategy imitates the N-terminal LANA binding conformation on nucleosomes.

Synthesis and biological evaluation of a MraY selective analogue of tunicamycins.
Kazuki Yamamoto; Toyotaka Sato; Yuta Hikiji; Akira Katsuyama; Takanori Matsumaru; Fumika Yakushiji; Shin-Ichi Yokota; Satoshi Ichikawa
Nucleosides, nucleotides & nucleic acids, 39, 1-3, 1, 16, 30 Sep. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Tunicamycins, which are nucleoside natural products, inhibit both bacterial phospho-N-acetylmuraminic acid (MurNAc)-pentapeptide translocase (MraY) and human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT). The improved synthesis and detailed biological evaluation of an MraY-selective inhibitor, 2, where the GlcNAc moiety was modified to a MurNAc amide, has been described.

Chemical logic of MraY inhibition by antibacterial nucleoside natural products
Ellene H. Mashalidis; Benjamin Kaeser; Yuma Terasawa; Akira Katsuyama; Do-Yeon Kwon; Kiyoun Lee; Jiyong Hong; Satoshi Ichikawa; Seok-Yong Lee
Nature Communication, 10, 1, 2917, 2917, Jul. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Novel antibacterial agents are needed to address the emergence of global antibiotic resistance. MraY is a promising candidate for antibiotic development because it is the target of five classes of naturally occurring nucleoside inhibitors with potent antibacterial activity. Although these natural products share a common uridine moiety, their core structures vary substantially and they exhibit different activity profiles. An incomplete understanding of the structural and mechanistic basis of MraY inhibition has hindered the translation of these compounds to the clinic. Here we present crystal structures of MraY in complex with representative members of the liposidomycin/caprazamycin, capuramycin, and mureidomycin classes of nucleoside inhibitors. Our structures reveal cryptic druggable hot spots in the shallow inhibitor binding site of MraY that were not previously appreciated. Structural analyses of nucleoside inhibitor binding provide insights into the chemical logic of MraY inhibition, which can guide novel approaches to MraY-targeted antibiotic design.

Structural requirement of tunicamycin V for MraY inhibition.
Yamamoto K; Katsuyama A; Ichikawa S
Bioorganic & medicinal chemistry, 27, 8, 1714, 1719, Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Elucidating a structure-activity relationship study by evaluating a series of truncated analogues is a simple but important and effective tactic in medicinal chemistry based on natural products with a large and complex chemical structure. In this study, a series of truncated analogues of tunicamycin V were designed and synthesized and their MraY inhibitory activity was investigated in order to gain insight into the effect of these moieties on MraY inhibition.

Total synthesis of plusbacin A3 using a diastereoseletive Joullié-Ugi three component reaction
Akira Katsuyama; Satoshi Ichikawa
Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 77, 7, 663, 672, Society of Synthetic Organic Chemistry, 2019
Japanese, Scientific journal

Total synthesis of plusbacin A3
Katsuyama Akira; Yakushiji Fumika; Ichikawa Satoshi
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 256, 19 Aug. 2018, [Peer-reviewed]

Total synthesis of plusbacin A3 and its dideoxy derivative using a solvent-dependent diastereodivergent Joullié–Ugi three-component reaction.
Katsuyama, Akira; Yakushiji, Fumika; Ichikawa, Satoshi
The Journal of Organic Chemistry, 83, 13, 7085, 7101, Feb. 2018, [Peer-reviewed], [Invited], [International Magazine]
English, Scientific journal, Full details of our synthetic studies toward plusbacin A3 (1), which is a depsipeptide with antibacterial activity, and its dideoxy derivative are described. To establish an efficient synthetic route of 1, a solvent-dependent diastereodivergent Joullié-Ugi three-component reaction (JU-3CR) was used to construct trans-Pro(3-OH) in a small number of steps. Two strategies were investigated toward the total synthesis. In the first synthetic strategy, the key steps were the trans-selective JU-3CR and a macrolactonization at the final stage of the synthesis. The JU-3CR using alkyl isocyanides in 1,1,1,3,3,3-hexafluoroisopropanol provided the trans products, and the coupling of the fragments to prepare the macrocyclization precursor proceeded smoothly. However, attempts toward the macrolactonization did not provide the desired product. Then, the second strategy that included esterification in an initial stage was investigated. Methods for constructing trans-Pro(3-OH) were examined using a convertible isocyanide, which could be converted to a carboxylic acid required for the following amidation. Ester bond formation was achieved through an intermolecular coupling using a hydroxyl-Asp derivative and the corresponding alcohol, and the amidation afforded a linear depsipeptide. The macrolactamization of the linear peptide gave the cyclic depsipeptide, and then the global deprotection accomplished the total synthesis of 1 and its dideoxy derivative.

Solid-Phase Modular Synthesis of Park Nucleotide and Lipids I and II Analogues.
Akira Katsuyama; Kousuke Sato; Fumika Yakushiji; Takanori Matsumaru; Satoshi Ichikawa
Chemical & pharmaceutical bulletin, 66, 1, 84, 95, 2018, [Peer-reviewed], [Lead author], [Domestic magazines]
English, Scientific journal, A solid-phase synthesis of Park nucleotide as well as lipids I and II analogues, which is applicable to the synthesis of a range of analogues, is described in this work. This technique allows highly functionalized macromolecules to be modularly labeled. Multiple steps are used in a short time (4 d) with a single purification step to synthesize the molecules by solid-phase synthesis.

Total Synthesis and Antibacterial Investigation of Plusbacin A(3)
Akira Katsuyama; Atmika Paudel; Suresh Panthee; Hiroshi Hamamoto; Toru Kawakami; Hironobu Hojo; Fumika Yakushiji; Satoshi Ichikawa
Organic Letters, 19, 14, 3771, 3774, Jul. 2017, [Peer-reviewed], [Lead author]
English, Scientific journal

Revisited Mechanistic Implications of the Joullie-Ugi Three-Component Reaction
Akira Katsuyama; Akira Matsuda; Satoshi Ichikawa
Organic Letters, 18, 11, 2552, 2555, Jun. 2016, [Peer-reviewed], [Lead author]
English, Scientific journal

Synthesis and Medicinal Chemistry of Muraymycins, Nucleoside Antibiotics
Akira Katsuyama; Satoshi Ichikawa
Chemical and Pharmaceutical Bulletin, 66, 2, 123, 131, Jan. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Muraymycins, isolated from a culture broth of Streptomyces sp., are members of a class of naturally occurring nucleoside antibiotics. They are strong inhibitors of the phospho-MurNAc-pentapeptide translocase (MraY), which is responsible for the peptidoglycan biosynthesis. Since MraY is an essential enzyme among bacteria, muraymycins are expected to be a novel antibacterial agent. In this review, our efforts to synthesize muraymycin D2, simplify the chemical structure, improve antibacterial spectrum, and solve the X-ray crystal structure of the muraymycin D2/MraY complex are described.

ジペプチドを用いたスキャニングによる新規ポリミキシン誘導体の創製研究
家口凜太郎; 勝山彬; 勝山彬; 佐藤豊孝; 堀内基広; 横田伸一; 市川聡; 市川聡, 創薬懇話会講演要旨集, 2022, 2022

Structure-activity relationship study of anti-P. aeruginosa active uridylpeptide natural products
寺澤侑馬; 佐高千里; 佐藤豊孝; 山本一貴; 勝山彬; 松丸尊紀; 松丸尊紀; 薬師寺文華; 横田伸一; 市川聡; 市川聡, 日本薬学会年会要旨集(Web), 141st, 2021

Rapid Construction of a Library of Polymyxin Analogue Using in situ Fragment Linking Strategy
家口凜太郎; 勝山彬; 佐藤豊孝; 横田伸一; 市川聡, 万有札幌シンポジウム, 32nd, 2020

ウリジルペプチド系天然物の構造活性相関研究
寺澤侑馬; 佐高千里; 佐藤豊孝; 山本一貴; 勝山彬; 松丸尊紀; 松丸尊紀; 薬師寺文華; 横田伸一; 市川聡; 市川聡, 反応と合成の進歩シンポジウム講演要旨集, 2020

ツニカマイシンVの全合成と低毒性誘導体の創製
山本一貴; 勝山彬; 薬師寺文華; 市川聡, 日本薬学会年会要旨集(CD-ROM), 139th, 2019

ツニカマイシンVの全合成と構造に基づく低毒性誘導体の創製
山本一貴; 勝山彬; 薬師寺文華; 松丸尊紀; 市川聡, 次世代を担う有機化学シンポジウム講演要旨集, 17th, 2019

Development of Positive Modulators of Histone H3K27 Methylation
Tokodai, Yasuaki; Yakushiji, Fumika; Sengoku, Toru; Katsuyama, Akira; Ichikawa, Satoshi, Peptide Science 2018, 14, 2018, [Peer-reviewed]
English, Introduction international proceedings

カルコゲン元素置換によるアミド化合物の結合回転制御
勝山 彬
第46回光化学若手の会, 15 Jun. 2025, Invited oral presentation
[Invited]

Development of a Structure Optimization Method for Bioactive Peptides
Akira Katsuyama
日本農芸化学会2025年度大会, 05 Mar. 2025, Invited oral presentation
[Invited]

立体選択的Joullié-Ugi三成分反応の反応機構解析
勝山 彬; 松田 彰; 市川 聡
日本薬学会第137年会, 27 Mar. 2017, Japanese, Oral presentation
[Domestic Conference]

Sythetic study of plusbacin A3
KATSUYAMA AKIRA; MATSUDA AKIRA; SATOSHI ICHIKAWA
第27回万有仙台シンポジウム, 25 Jun. 2016, Japanese, Poster presentation
[Invited], [Domestic Conference]

Sythetic study of plusbacin A3
KATSUYAMA AKIRA; ICHIKAWA SATOSHI
第14回次世代を担う有機化学シンポジウム, 27 May 2016, Japanese, Oral presentation
[Domestic Conference]

Synthetic study of plusbacin A3
KATSUYAMA AKIRA
The 2015 International Chemical Congress of Pacific Basin Societies, 15 Dec. 2015, English, Poster presentation
[International presentation]

Synthetic study of plusbacin A3
KATSUYAMA AKIRA; MATSUDA AKIRA; ICHIKAWA SATOSHI
The 52nd Japanese Peptide Symposium, 16 Nov. 2015, English, Oral presentation
[Domestic Conference]

Synthetic study of plusbacin A
KATSUYAMA AKIRA; MATSUDA AKIRA; ICHIKAWA SATOSHI
第27回札幌万有シンポジウム, 04 Jul. 2015, Japanese, Poster presentation
[Domestic Conference]

Synthetic study of plusbacin A3
KATSUYAMA AKIRA; MATSUDA AKIRA; ICHIKAWA SATOSHI
日本薬学会第135年会, 28 Mar. 2015, Japanese, Oral presentation
[Domestic Conference]

Synthetic study of plusbacin A
KATSUYAMA AKIRA; MATSUDA AKIRA; ICHIKAWA SATOSHI
The 2nd International Symposium on AMBITIOUS LEADER’S PROGRAM Fostering Future Leaders to Open New Frontiers in Material Science, 11 Dec. 2014, English, Poster presentation
[International presentation]

Synthetic Studies of plusbacin A3
KATSUYAMA AKIRA; MATSUDA AKIRA; ICHIKAWA SATOSHI
第56回天然有機化合物討論会, 16 Oct. 2014, Japanese, Poster presentation
[Domestic Conference]

Plusbacin A3の合成研究
勝山 彬; 松田彰; 市川聡
日本薬学会北海道支部第141例会, 24 May 2014, Japanese, Oral presentation
[Domestic Conference]

Diastereo-controlled synthesis of 3-hydroxyproline derivatives via Ugi three-component reaction and its application for total synthesis of plusbacin A3
KATSUYAMA AKIRA; MATSUDA AKIRA; ICHIKAWA SATOSHI
日本薬学会第134年会, 28 Mar. 2014, Japanese, Oral presentation
[Domestic Conference]

創薬化学特論, 2024年, 修士課程, 生命科学院

先端生物科学実験法Ⅰ, 2024年, 学士課程, 薬学部

有機化学Ⅴ, 2024年, 学士課程, 薬学部

有機化学実習Ⅴ, 2024年, 学士課程, 薬学部

有機化学実習Ⅵ, 2024年, 学士課程, 薬学部

ドラッグデザイン演習, 2024年, 学士課程, 薬学部

有機化学Ⅵ, 2024年, 学士課程, 薬学部

配座・機能制御を基盤とした分子スイッチ医薬品の論理的設計
戦略的な研究開発の推進 創発的研究支援事業
2025 - 2032
勝山 彬
医薬品は、標的分子に結合する性質、体内動態に関する性質など、複数の機能が然るべき時と場所で発現することではじめて有効に機能します。本研究では、医薬品候補となりうる「有機化合物の形」に着目し、これらの複数の機能の発現を自在に制御できる革新的な医薬品を開発するための方法論を開発します。独自の分子スイッチ活用し、疾患の原因となる標的分子の3次元構造に基づいた論理的な分子設計を通じて研究目的の達成を目指します。
科学技術振興機構, 北海道大学, Principal investigator

構造-レジデンスタイム相関の解明と制御
科学研究費助成事業
Apr. 2025 - Mar. 2029
市川 聡; 勝山 彬
日本学術振興会, 基盤研究(A), 北海道大学, Coinvestigator, 25H01014

活性配座の記憶と固定化に基づく創薬方法論の開発
科学研究費助成事業
27 Jun. 2025 - 31 Mar. 2027
市川 聡; 勝山 彬
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 25K22512

多段階修飾・構造制御を可能とする新規ペプチドスキャニング法の開発
科学研究費助成事業
01 Apr. 2024 - 31 Mar. 2027
勝山 彬
日本学術振興会, 基盤研究(C), 北海道大学, 24K09703

Development of a novel Antibody-drug conjugate for cancer therapy
Grants-in-Aid for Scientific Research
01 Apr. 2024 - 31 Mar. 2027
鍛代 悠一; 勝山 彬
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24K09810

ビルドアップライブラリー構築法を用いた薬剤耐性菌リードの創出研究
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
市川 聡; 勝山 彬
日本学術振興会, 基盤研究(B), 北海道大学, 22H02738

レジデンスタイム制御構造要素探索とその制御による薬物設計理論の提唱
科学研究費助成事業
Jun. 2023 - Mar. 2025
市川 聡; 勝山 彬
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, Coinvestigator, 23K18171

ビルドアップライブラリー構築法を用いた薬剤耐性菌リードの創出研究
科学研究費助成事業
Apr. 2022 - Mar. 2025
市川 聡; 勝山 彬
天然物は人智を超えた活性・構造を有する重要な創薬シード分子である。中分子天然物を創薬リードへと昇華させるためには、包括的な天然物誘導体から構成されるライブラリーの構築は極めて大きな意義を持つ。申請者はこれまで、迅速かつ網羅的な中分子天然物ライブラリーの合成を可能とする「ビルドアップライブラリー構築」とその直接生物活性評価スキームを開発してきた。本申請研究では、本法を更に創薬リード創出に資する強力な中分子天然物創薬プラットホームとすべく、さらに①標的とする天然物とアクセサリーの拡充と、②様々な生物学的等価体に変換と構造最適化を行う事で、創薬リード創出を図る。令和4年度は、コリスチン、リファンピシン、ツニカマイシン、ムレイドマイシン等のビル負度アップライブラリーを作製した。更にその直接の生物活性評価を迅速に行う事により、コリスチン、ツニカマイシン、ムレイドマイシンの３つについては、もとの天然物の生物活性を凌駕する誘導体を同定する事が出来た。また、ムライマイシンについては、連結部であるヒドラゾン構造を、化学的・生物学的により安定な結合に変換した誘導体も合成し、in vitroでの生物活性の向上と、in vivoで薬理活性を発現する誘導体の同定に至っている。コリスチンに関する論文は、既にJ. Am. Chem. Soc.にて公表されている。ムライマイシンに関する研究については、論文投稿中である。
日本学術振興会, 基盤研究(B), 北海道大学, Coinvestigator, 23K24001

多成分連結型天然物ビルドアップライブラリー法の確立
科学研究費助成事業
Apr. 2022 - Mar. 2024
勝山 彬
日本学術振興会, 若手研究, 北海道大学, Principal investigator, 22K15241

Development of Antibacterial Natural Products Derivatives
Grants-in-Aid for Scientific Research
Apr. 2019 - Mar. 2021
Katsuyama Akira
A reserch based on natural products with antimicrobial activity was conducted to develop novel antimicrobial agents which are effective against drug-resistant bacteria. We focused on empedopeptin, which is natural product that inhibit bacterial cell wall biosynthesis. Thus, synthetic research of empedopeptin was conducted. We also synthesized lipid II and its related compounds, which are precursors of a bacterial cell wall, to elucidate the mechanism of action of the natural products. As a result, fluorescent probe molecules were synthesized.
Japan Society for the Promotion of Science, Grant-in-Aid for Early-Career Scientists, Hokkaido University, Principal investigator, 19K16308

Development of a quick and simple search method for active conformations with amplification and memory of active conformations as the key concept
Grants-in-Aid for Scientific Research
Jun. 2018 - Mar. 2021
Ichikawa Satoshi
First, an indomethacin derivative having a substituent at the ortho positions of the benzene ring was synthesized and mixed with various proteins at 37 ° C. for 24 hours. As a result, a slight asymmetric amplification was observed when catalase was used. Next, we focused on the fact that the benzamide structure, which is a structure widely found in drugs, has two axial asymmetry of C-C bond and C-N bond, and investigated the properties of bond rotation. As a result, it was found that the type of substituent at the ortho position of the benzene ring shows the slow interconversion property characteristic of the atropisomer at a wide range of substituents, although the rotational speeds of both axes are slightly changed. Furthermore, this property was applied to enzyme inhibitors such as WDR5 inhibitors and HDAC inhibitors.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, Coinvestigator, 18K19384

天然物のフラグメント化を基軸とした抗菌薬の開発研究
科学研究費助成事業
Aug. 2018 - Mar. 2020
勝山 彬
薬剤耐性菌に対して有効かつ、薬剤耐性が生じにくい新規抗菌薬を開発することを目的として、申請者の研究により薬剤耐性が生じにくいことが明らかとなった天然物、プラスバシンA3を基盤とした創薬化学研究を実施した。この際、本天然物が環状ペプチド部と脂溶性側鎖部という異なる部分構造からなり、それぞれの部分構造が独立して作用するという作用機序に注目し、アッセイ直前に両フラグメントをアシルヒドラゾンで連結する、アッセイ前合成を利用することとし、本手法の確立を目指し研究を実施した。申請者がこれまでに確立した液相合成法に基づき、固相合成法の確立に向けた検討を行った。固相合成に必要となるアミノ酸ユニットのうち、ヒドロキシアスパラギン酸、trans-3-ヒドロキシプロリン残基については対応するFmoc保護アミノ酸が必要となるが、ヒドロキシアスパラギン酸については、アスパギン酸を出発物質として6工程の変換により、必要な両エナンチオマーを合成した。trans-3ヒドロキシプロリンについては、申請者が開発したジアステレオ選択的Joullie-Ugi 三成分反応と2工程の変換により、ジペプチドユニットとして合成した。脂溶性側鎖部分は、後にアシルヒドラジンないしはアルデヒドへと変換可能なアルキンを導入したものを合成することとし、対応するユニットの合成を完了した。次に、合成したそれぞれのユニットを用いてペプチド固相合成を検討し、環化前駆体を合成した。
日本学術振興会, 研究活動スタート支援, 北海道大学, Principal investigator, 18H06098

多成分反応とアルキンスキャニング法を基盤とする新規抗菌薬の開発研究
科学研究費助成事業
Apr. 2017 - Mar. 2019
勝山 彬
薬剤耐性菌に有効な新規抗菌薬の開発にあたり、天然物であるプラスバシンA3をリードとした創薬科学研究を行うことを計画し、まずはプラスバシンA3の全合成を行った。効率的な合成法開発のために、三成分縮合反応を本化合物の合成の鍵反応として選択し、この反応を２度用いることで、プラスバシンA3の高効率的な合成経路を確立した。次に、合成したプラスバシンA3の抗菌薬としての性質を評価した。合成したプラスバシンA3は、薬剤耐性菌を含む各種黄色ブドウ球菌に対して強力な抗菌活性を示した。さらに、本化合物に対する薬剤耐性がどの程度生じうるのかを実験的に調査した。その結果、プラスバシンA3に対する耐性は25日後においても約8倍に抑制されており、これは薬剤耐性が生じにくいことが知られている抗菌薬である、バンコマイシンに匹敵するものであることが明らかとなった。薬剤耐性が生じにくい抗菌薬を開発することができれれば、これまでの抗菌薬の歴史である、新薬の開発と薬剤耐性菌の出現という、いわば、いたちごっこの状況に変化をもたらすことが可能となる。すなわち、一つの抗菌薬を長期間に渡り有効な状態に保つことで、感染症の脅威から、人々を長期的に守ることができる。プラスバシンA3はそのような抗菌薬のリードとして有用であることが本研究の結果示されたため、今後さらなる研究の継続により、本化合物の誘導体が新規抗菌薬として開発されることが期待できる。
日本学術振興会, 特別研究員奨励費, 北海道大学, 17J04794

Development of drug leads for drug-resistance bacterial pathogens based on natural products
Grants-in-Aid for Scientific Research
Apr. 2016 - Mar. 2019
Satoshi Ichikawa; Katsuyama Akira; Sato Toyotaka; Lee Seok-Yong
1)Synthesis and biological evaluation of muraimycin analogues were investigated. 2) Synthesis of the core structure of phaerimycin and its derivatives was achieved and their MraY inhibitory activity was also conducted. As a result, one derivative showed high MraY inhibitory activity. 3) Mureidomycin A analigues were synthesized and it was found that some derivatives exhibited higher MraY inhibitory activity and anti-P. aeruginosa activity than pacidamycin D, which is a conger of mureidomycin A. Furthermore, X-ray crystal structure analysis of the complex of mureidomycin analogue bound to MraY was also established. 4) The synthesis and action mechanism analysis of plasbacin A3 and its derivative were conducted. 5) In order to find an effective derivative against colistin resistant bacteria, 30 colistin derivatives were synthesized and their antibacterial activities were evaluated.
Some drug resistant bacterial drug lead were developed in this study.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16H05097