Wiley Acta Medica Okayama 2367-0932 10 7 2026 Photochemical Oxidative Esterification of Aldehydes with Radical-Sensitive Alcohols via CH Bromination e70221 EN Nova Alfian Hariyanto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haru Ando Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsuya Miyamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photochemical esterification is an attractive strategy for the synthesis of multifunctionalized esters, and the use of aldehydes as substrates offers an alternative to conventional carboxylic acid–based approaches. In particular, reactions via acyl halide intermediates are useful for accessing functionalized esters; however, examples of such transformations remain limited so far, and their compatibility with radical-sensitive alcohols remains relatively unexplored. Here, we report a photochemical oxidative esterification of aldehydes with radical-sensitive alcohols enabled by CH bromination. This reaction proceeds without stoichiometric additives, such as bases, and enables the incorporation of a broad range of radical-sensitive functional groups into esters. Thus, it represents a promising platform for the synthesis of pharmaceuticals and functional materials. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 22 46 2024 A direct oxidative esterification of aldehydes with alcohols mediated by photochemical C–H bromination 9032 9035 EN Haru Ando Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Sakura Kodaki Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University The photochemical direct esterification of aldehydes with alcohols via in situ-generated acyl-bromides presented in this report is an attractive complementary addition to hitherto reported methods, as these are usually carried out in a two-step, one-pot procedure in order to avoid side reactions such as the oxidation of alcohols by halogen sources. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0040-4039 183 2026 Photochemical oxidative synthesis of carboxylic acids from aldehydes or alcohols with water via CH bromination 156163 EN Mohamed R. El-kholany Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Atsuya Miyamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Morgane Falcone Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The photoinduced oxidation of aldehydes or alcohols with water to give the corresponding carboxylic acids is described. This photochemical carboxylation proceeds via the in-situ generation of acyl-bromide intermediates upon irradiation with purple or UV LED light; these intermediates subsequently react with water to give the desired carboxylic acids. This mild photochemical reaction affords diverse carboxylic acids without peroxide generation or the need to use transition-metal catalysts and a stoichiometric amount of base, highlighting its potential utility for the synthesis of natural products and bioactive compounds. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-951X 19 2026 Heteroarylation of mono- and dichloroarenes via phenothiazine organophotoredox catalysis 100163 EN Masato Oishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University 2-Arylpyrroles are key structural motifs found in a wide range of pharmaceuticals and functional materials. Although the photocatalytic heteroarylation of pyrroles with aryl iodides and bromides has been extensively developed for the synthesis of 2-arylpyrroles, the corresponding reactions using aryl chlorides remain relatively unexplored owing to the high energy barrier associated with C(sp2)–Cl bond activation. Herein, we report a phenothiazine-based organophotoredox-catalyzed heteroarylation of aryl chlorides with pyrroles for the synthesis of diverse 2-arylpyrroles. Notably, dichloroarenes also efficiently undergo heteroarylation to afford the corresponding products. Therefore, the present reaction represents a versatile approach to heteroarylation and provides a valuable tool for the synthesis of pharmaceuticals and functional materials. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 2026 Synthesis of sulfur- and oxygen-bridged cationic [4]-helicenes mediated by Friedel–Crafts-S _N Ar tandem reactions for red-light-driven organophotoredox catalysis EN Ryoga Hasebe Graduate School of Environment and Information Sciences, Yokohama National University Rumi Hanada Graduate School of Environment and Information Sciences, Yokohama National University Yuta Tanaka Graduate School of Environment and Information Sciences, Yokohama National University Yuta Goto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mio Takeuchi Graduate School of Environment and Information Sciences, Yokohama National University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Yujiro Hoshino Graduate School of Environment and Information Sciences, Yokohama National University The synthesis of sulfur- and oxygen-bridged cationic [4]-helicenes via a tandem Friedel–Crafts–SNAr reaction of a diaryl sulfide or a diaryl ether with a (thio)salicylic acid has been developed. The sulfur-bridged cationic [4]-helicenes are suitable as catalysts for photoredox reactions under low-energy light sources such as red LED light. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0040-4039 179 2026 Visible-light-induced photocatalytic intermolecular cyclization for synthesis of 2,2-diarylchromanes 156034 EN Sakura Kodaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Momo Kondo Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Junta Minato Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science Shoko Itakura Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Makiya Nishikawa Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kosuke Kusamori Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University The photocatalytic cyclization of salicylaldehydes with 1,1-diarylalkenes for the synthesis of 2,2-diarylchromanes has been developed. The catalytic amount of Ir photocatalyst proceeds the cyclization to give the various 2,2-diaryl chromanes under irradiation with blue LEDs. The obtained 2,2-diarylchromanes exhibit noticeable free-radical-scavenging activities, which have been largely unexplored. Notably, the chromane can convert to 2,2-diaryl-2H-naphtho[1,2-b]pyran bearing strong electron withdrawing groups, which are found in various photochromic materials. Thus, the present reaction constitutes a promising tool for the synthesis of functional materials and biologically active compounds. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2771-9316 2025 Photochemical Macrolactonization of Hydroxyaldehydes via C–H Bromination EN Sakura Kodaki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haru Ando Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 61 89 2025 The direct photochemical cross-esterification of alcohols via site-selective C–H bromination site-selective C–H bromination 17364 17367 EN Atsuya Miyamoto Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University We have developed a direct photochemical cross-esterification of alcohols that proceeds via the in situ generation of acyl bromides. The C–H bond of a benzyl alcohol is selectively activated by a bromo source under light irradiation, enabling the cross-esterification to afford a variety of functionalized esters. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 2025 Generation of alkyl radicals via C(sp3)–C(sp3) bond cleavage of xanthene-based precursors for photocatalytic Giese-type reaction EN Shuta Horiuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Masato Oishi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Asuka Mizutani Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Novel xanthene-based alkyl radical precursors were developed and subjected to photocatalytic C(sp3)–C(sp3) bond cleavage for the efficient generation of alkyl radicals, which were subsequently reacted with various alkenes to afford the corresponding Giese-type products. After the reaction, the produced xanthones can be recovered in high yield. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0009-2673 98 6 2025 Redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes for the regio- and diastereoselective synthesis of multisubstituted halogenocyclobutanes uoaf044 EN Asuka Mizutani Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Momo Kondo Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Shoko Itakura Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yujiro Hoshino Graduate School of Environment and Information Sciences, Yokohama National University Makiya Nishikawa Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kosuke Kusamori Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University The redox potential is an important factor for controlling the outcome of photoredox catalysis. Particularly, the selective oxidation of substrates and the control over the reactions are challenging when using photoredox catalysts that have high excited-state reduction potentials. In this study, a redox-potential-controlled intermolecular [2 + 2] cycloaddition of styrenes using a thioxanthylium organophotoredox (TXT) catalyst has been developed. This TXT catalyst selectively oxidizes β-halogenostyrenes and smoothly promotes the subsequent intermolecular [2 + 2] cycloadditions to give multisubstituted halogenocyclobutanes with excellent regio- and diastereoselectivity, which has not been effectively achieved by the hitherto reported representative photoredox catalysts. The synthesized halogenocyclobutanes exhibit interesting free radical scavenging activity. The present reaction contributes to the field of redox-potential-controlled electron transfer chemistry. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0040-4039 169 2025 Recent progress on phenothiazine organophotoredox catalysis 155745 EN Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Hiroyoshi Takamura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Isao Kadota Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Photoredox catalysis has garnered significant attention in recent years due to its broad applicability in visible-light-induced organic transformations. While significant progress has been made in the development of highly oxidizing catalysts, such as acridinium catalysts, there remains a notable shortage of strongly reducing organophotoredox catalysts. Phenothiazines are widely used as photoredox catalysts owing to their unique redox potentials, particularly their low excited-state oxidation potentials (Eox* = −1.35 V to −3.51 V vs. SCE). Thus, they can be applied to a variety of photoredox reactions with oxidative-quenching cycles, and effectively reduce various organic molecules, such as aryl and alkyl halides, alkenes, malonyl peroxides, cobalt complexes, and redox-active esters. Due to their unique properties, this review focuses on the recent advances in phenothiazine organophotoredox catalysis. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1612-1872 2025 Antifouling Activity of Xylemin, Its Structural Analogs, and Related Polyamines e202403213 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takefumi Yorisue Institute of Natural and Environmental Sciences, University of Hyogo Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Biofouling, which is the accumulation of organisms on undersea structures, poses significant global, social, and economic issues. Although organotin compounds were effective antifoulants since the 1960s, they were banned in 2008 due to their toxicity to marine life. Although tin-free alternatives have been developed, they also raise environmental concerns. This underscores the need for effective, nontoxic antifouling agents. We previously synthesized N-(4-aminobutyl)propylamine (xylemin) and its structural analogs. In this study, we assayed the antifouling activity and toxicity of xylemin, its structural analogs, and related polyamines toward cypris larvae of the barnacle Amphibalanus amphitrite. Xylemin and its Boc-protected analog exhibited antifouling activities with 50% effective concentrations (EC50) of 4.25 and 6.11 µg/mL, respectively. Four xylemin analogs did not show a settlement-inhibitory effect at a concentration of 50 µg/mL. Putrescine, spermidine, spermine, and thermospermine, which are xylemin-related polyamines, did not display antifoulant effects (EC50 > 50 µg/mL). All evaluated compounds were nontoxic at a concentration of 50 µg/mL. These findings indicate that the size and structure of the N-alkyl group are essential for the antifouling activity of xylemin. Therefore, xylemin and its analogs hold promise as nontoxic, eco-friendly antifouling agents, offering a sustainable solution to biofouling in marine environments. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 22 28 2024 Total synthesis and structure–antifouling activity relationship of scabrolide F 5739 5747 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yuki Sugitani Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Ryohei Morishita Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takefumi Yorisue Institute of Natural and Environmental Sciences, University of Hyogo Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University An efficient synthetic strategy for scabrolide F (7), a norcembranolide diterpene that was isolated from the Taiwanese soft coral Sinularia scabra, has only recently been reported by our group. Herein, we report details of the first total synthesis of 7. The tetrahydrofuran domain of 7 was stereoselectively constructed via the 5-endo-tet cyclization of a hydroxy vinyl epoxide. The reaction of alkyl iodide 30 with dithiane 38, followed by the introduction of an alkene moiety, afforded allylation precursor 41. The coupling of alkyl iodide 42 and allylic stannane 43 was examined as a model experiment of allylation. Because the desired allylated product 44 was not obtained, an alternative synthetic route toward 7 was investigated instead. In the second synthetic approach, fragment–coupling between alkyl iodide 56 and aldehyde 58, macrolactonization, and transannular ring-closing metathesis were used as the key steps to achieve the first total synthesis of 7. We hope that this synthetic strategy provides access to the total synthesis of other macrocyclic norcembranolides. We also evaluated the antifouling activity and toxicity of 7 and its synthetic intermediates toward the cypris larvae of the barnacle Amphibalanus amphitrite. This study is the first to report the antifouling activity of norcembranolides as well as the biological activity of 7. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2023 Relative stereochemical determination of the C61–C83 fragment of symbiodinolide using a stereodivergent synthetic approach EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Kosuke Hattori Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takumi Ohashi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Taichi Otsu Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Structural determination is required in the use of marine natural products to create novel drugs and drug leads in medicinal chemistry. Symbiodinolide, which is a polyol marine natural product with a molecular weight of 2860, increases the intracellular Ca2+ concentration and exhibits inhibitory activity against cyclooxygenase-1. Seventy percent of the structure of symbiodinolide has been stereochemically clarified. Herein, we report the elucidation of the relative configuration of the C61–C83 fragment, which is among the remaining thirty percent, using a stereodivergent synthetic strategy. We first assigned the relative configuration of the C61–C74 fragment. Two candidate diastereomers of the C61–C74 fragment were synthesized, and their NMR data were compared with those of the natural product, revealing the relative stereochemistry of this component. We then narrowed down the candidate compounds for the C69–C83 fragment from 16 possible diastereomers by analyzing the NMR data of the natural product, and we thus selected eight candidate diastereomers. Stereodivergent synthesis of the candidates for this fragment and comparison of the NMR data of the natural product and the eight synthetic products resulted in the relative stereostructural clarification of the C69–C83 fragment. These individually determined relative stereochemistries of the C61–C74 and C69–C83 fragments were connected via the common C69–C73 tetrahydropyran moiety of the fragments. Finally, the relative configuration of the C61–C83 fragment of symbiodinolide was determined. The stereodivergent synthetic approach used in this study can be extended to the stereochemical determination of other fragments of symbiodinolide. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 21 3 2022 Chemical synthesis and antifouling activity of monoterpene–furan hybrid molecules 632 638 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yuya Kinoshita Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takefumi Yorisue Institute of Natural and Environmental Sciences, University of Hyogo Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Geraniol, a monoterpene, and furan are structural motifs that exhibit antifouling activity. In this study, monoterpene-furan hybrid molecules with potentially enhanced antifouling activity were designed and synthesized. The nine synthetic hybrids showed antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC50 values of 1.65-4.70 mu g mL(-1). This activity is higher than that of geraniol and the reference furan compound. This hybridization approach to increase antifouling activity is useful and can also be extended to other active structural units. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1523-7060 24 42 2022 Total Synthesis of Scabrolide F 7845 7849 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yuki Sugitani Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Ryohei Morishita Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University The first total synthesis of scabrolide F, a norcembranolide isolated from the soft coral Sinularia scabra, is described. Hydroxycarboxylic acid, which is the key synthetic intermediate, was synthesized in a convergent manner by fragment coupling. The obtained hydroxycarboxylic acid was subjected to macrolactonization and subsequent transannular ring-closing metathesis (RCM) to furnish scabrolide F. The synthetic protocol can be extended to the total synthesis of other norcembranolides. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1434193X 2020 18 2020 Chemical Synthesis and Biological Effect on Xylem Formation of Xylemin and Its Analogues 2745 2753 EN Hiroyoshi Takamura Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Hiroyasu Motose Graduate School of Natural Science and Technology, Okayama University Taichi Otsu Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Shiori Shinohara Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Ryugo Kouno Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Taku Takahashi Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Xylemin (6 ) and its designed structural analogues 18 –23 , N ‐(4‐aminobutyl)alkylamines, were synthesized by 2‐nitrobenzenesulfonamide (Ns) strategy. Investigation of the improved synthesis of 20 –23 resulted in the development of one‐step synthesis of these analogues from the commercially available corresponding ketones. Biological assessment of the synthetic molecules elucidated that xylemin (6 ) and the analogue N ‐(4‐aminobutyl)cyclopentylamine (21 ) promoted the expression level of thermospermine synthase ACAULIS5 (ACL5 ) and enhanced xylem formation. In addition, xylemin (6 ) was found to significantly promote lateral root formation, whereas xylemin analogues 18 –23 including 21 did not. These results indicate that the analogue 21 has the potential as a novel inhibitor of thermospermine synthesis to work specifically in xylem differentiation. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 0022-3263 83 18 2018 Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides 11028 11056 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Takahiro Kikuchi Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Kohei Iwamoto Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Eiji Nakao Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Naoki Harada Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Taichi Otsu Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Noriyuki Endo Himeji EcoTech Co., Ltd. Yuji Fukuda Himeji EcoTech Co., Ltd. Osamu Ohno Department of Chemistry and Life Science, School of Advanced Engineering , Kogakuin University Kiyotake Suenaga Department of Chemistry, Faculty of Science and Technology , Keio University Yue-Wei Guo Shanghai Institute of Materia Medica , Chinese Academy of Sciences Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology , Okayama University Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of genus Sarcophyton. Unified total synthesis of sarcophytonolides C, E, F, G, H, and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS- or SmI2-mediated fragment coupling, alkoxycarbonylallylation, macrolactonization, and transannular ring-closing metathesis. These total syntheses led to the absolute configurational confirmation of sarcophytonolide H, elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide J and isosarcophytonolide D. We also evaluated the antifouling activity and toxicity of the synthetic sarcophytonolides H and J and their analogues as well as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic intermediates. No potential conflict of interest relevant to this article was reported.

Pergamon Press Acta Medica Okayama 00404039 59 11 2018 Recent topics of the stereodivergent synthesis of natural products 955 966 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University A variety of natural products, a valuable source of drug lead compounds, coexist with their stereoisomers as congeners. For pursuing the structural elucidation and the structure–activity relationship study of natural products, it is needed to establish the streamlined synthetic route to supply natural products and their stereoisomers. Divergent pathway is one of the synthetic strategies to deliver more than one target compound. In this digest, selected examples of the stereodivergent approach toward the synthesis of natural products are described. Especially, this digest focuses on common synthetic intermediates and stereodiversification steps from the common intermediates to reach the target compounds. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 00223263 80 6 2015 Stereodivergent synthesis and relative stereostructure of the C1-C13 fragment of symbiodinolide 3111 3123 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroko Wada Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Mao Ogino Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takahiro Kikuchi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Daisuke Uemura Department of Chemistry, Faculty of Science, Kanagawa University Four possible diastereomers of the C1-C13 fragment of symbiodinolide, which were proposed by the stereostructural analysis of the degraded product, were synthesized in a stereodivergent and stereoselective manner. The key transformations were aldol reaction of methyl acetoacetate with the aldehyde, diastereoselective reduction of the resulting β-hydroxy ketone, and the stereoinversion at the C6 position. Comparison of the (1)H NMR data between the four synthetic products and the degraded product revealed the relative stereostructure of the C1-C13 fragment of symbiodinolide. No potential conflict of interest relevant to this article was reported.

WILEY‐VCH Acta Medica Okayama 0947-6539 22 6 2016 Stereodivergent Synthesis and Stereochemical Reassignment of the C79-C104 Fragment of Symbiodinolide 1984 1996 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takayuki Fujiwara Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yohei Kawakubo Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Daisuke Uemura Department of Chemistry, Faculty of Science, Kanagawa University We have synthesized eight possible diastereoisomers 3 a-h of the C79-C97 fragment of symbiodinolide (1) in a stereodivergent manner by utilizing a dithiane addition to the aldehyde as a key step. Comparison of the 13 C NMR chemical shifts of the natural product 1 and the synthetic products 3 a-h indicated that the relative stereostructure of this fragment in symbiodinolide (1) is that represented in 3 a or f. We have stereodivergently synthesized eight possible diastereoisomers of the C94-C104 fragment 4 a-h, and we have compared their 13 C NMR chemical shifts with those of the natural product, which established the relative stereochemistry of this fragment to be that described in diastereoisomers 4 a or e. By combining the stereostructural outcomes of the C79-C97 and C94-C104 fragments, we have proposed four candidate compounds of the C79-C104 fragment 2 a-d. We also synthesized diastereoisomers 2 a and b (2 a in the preceding article; Chem. Eur. J. 2015, DOI: 10.1002/chem.201503880) by a Julia-Kocienski olefination and diastereoisomers 2 c and d by a Wittig reaction. By comparing the 13 C NMR chemical shifts of natural symbiodinolide (1) with those of the synthetic products 2 a-d, we have reassigned the stereostructure of the C79-C104 fragment of natural product 1 to be that depicted in diastereoisomer 2 b. No potential conflict of interest relevant to this article was reported.

Wiley-VCH Acta Medica Okayama 0947-6539 22 6 2016 Stereoselective Synthesis of the Proposed C79-C104 Fragment of Symbiodinolide 1979 1983 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takayuki Fujiwara Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Yohei Kawakubo Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Daisuke Uemura Department of Chemistry, Faculty of Science, Kanagawa University Stereoselective and streamlined synthesis of the proposed C79-C104 fragment 2 of symbiodinolide (1), a polyol marine natural product with a molecular weight of 2860, was achieved. In the synthetic route, the proposed C79-C104 fragment 2 was synthesized by utilizing a Julia-Kocienski olefination and subsequent Sharpless asymmetric dihydroxylation as key transformations in a convergent manner. Detailed comparison of the 13 C NMR chemical shifts between the natural product and the synthetic C79-C104 fragment 2 revealed that the stereostructure at the C91-C99 carbon chain moiety of symbiodinolide (1) should be reinvestigated. No potential conflict of interest relevant to this article was reported.

American Chemical Society Acta Medica Okayama 15237060 18 9 2016 Total Synthesis of Sarcophytonolide H and Isosarcophytonolide D: Structural Revision of Isosarcophytonolide D and Structure-Antifouling Activity Relationship of Sarcophytonolide H 2110 2113 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takahiro Kikuchi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Noriyuki Endo Himeji EcoTech Co., Ltd. Yuji Fukuda Himeji EcoTech Co., Ltd. Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University The first total syntheses of sarcophytonolide H and the originally proposed and correct structures of isosarcophytonolide D have been achieved via transannular ring-closing metathesis (RCM). These total syntheses culminated in the stereostructural confirmation of sarcophytonolide H and the reassignment of isosarcophytonolide D, respectively. The antifouling activity of the synthetic sarcophytonolide H and its analogues was also evaluated. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 14770520 15 26 2017 Late-stage divergent synthesis and antifouling activity of geraniol-butenolide hybrid molecules 5549 5555 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takumi Ohashi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takahiro Kikuchi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Noriyuki Endo Himeji EcoTech Co., Ltd. Yuji Fukuda Himeji EcoTech Co., Ltd. Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Hybrid molecules consisting of geraniol and butenolide were designed and synthesized by the late-stage divergent strategy. In the synthetic route, ring-closing metathesis was utilized for the construction of a butenolide moiety. A biological evaluation of the eight synthetic hybrid compounds revealed that these molecules exhibit antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC50 values of 0.30-1.31 μg mL-1. These results show that hybridization of the geraniol and butenolide structural motifs resulted in the enhancement of the antifouling activity. No potential conflict of interest relevant to this article was reported.

Wiley‐VCH Acta Medica Okayama 09476539 23 68 2017 Total Synthesis of Two Possible Diastereomers of Natural 6-Chlorotetrahydrofuran Acetogenin and Its Stereostructural Elucidation 17191 17194 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Tomoya Katsube Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Kazuki Okamoto Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University The first total synthesis of two possible diastereomers of natural 6-chlorotetrahydrofuran acetogenin 1 has been achieved. The synthetic route features 5-exo-tet cyclization, Z selective Wittig reaction and Julia olefination for the construction of conjugated diene and enyne moieties, and stereoselective chlorination. Comparison of their 1 H and 13 C NMR data and specific rotation with those of the natural product elucidated the absolute configuration of natural (-)-6-chlorotetrahydrofuran acetogenin 1. No potential conflict of interest relevant to this article was reported.

Nature Publishing Acta Medica Okayama 2045-2322 6 2016 Chemical control of xylem differentiation by thermospermine, xylemin and auxin 21487 EN Kaori Yoshimoto Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Hiroyasu Motose Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Taku Takahashi Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University The xylem conducts water and minerals from the root to the shoot and provides mechanical strength to the plant body. The vascular precursor cells of the procambium differentiate to form continuous vascular strands, from which xylem and phloem cells are generated in the proper spatiotemporal pattern. Procambium formation and xylem differentiation are directed by auxin. In angiosperms, thermospermine, a structural isomer of spermine, suppresses xylem differentiation by limiting auxin signalling. However, the process of auxin-inducible xylem differentiation has not been fully elucidated and remains difficult to manipulate. Here, we found that an antagonist of spermidine can act as an inhibitor of thermospermine biosynthesis and results in excessive xylem differentiation, which is a phenocopy of a thermospermine-deficient mutant acaulis5 in Arabidopsis thaliana. We named this compound xylemin owing to its xylem-inducing effect. Application of a combination of xylemin and thermospermine to wild-type seedlings negates the effect of xylemin, whereas co-treatment with xylemin and a synthetic proauxin, which undergoes hydrolysis to release active auxin, has a synergistic inductive effect on xylem differentiation. Thus, xylemin may serve as a useful transformative chemical tool not only for the study of thermospermine function in various plant species but also for the control of xylem induction and woody biomass production. No potential conflict of interest relevant to this article was reported.

Macmillan Publishers Limited. Acta Medica Okayama 2045-2322 6 2016 Chemical control of xylem differentiation by thermospermine, xylemin, and auxin 21487 EN Kaori Yoshimoto Hiroyoshi Takamura Isao Kadota Hiroyasu Motose Department of Biological Science, Graduate School of Natural Science and Technology, Okayama University Taku Takahashi The xylem conducts water and minerals from the root to the shoot and provides mechanical strength to the plant body. The vascular precursor cells of the procambium differentiate to form continuous vascular strands, from which xylem and phloem cells are generated in the proper spatiotemporal pattern. Procambium formation and xylem differentiation are directed by auxin. In angiosperms, thermospermine, a structural isomer of spermine, suppresses xylem differentiation by limiting auxin signalling. However, the process of auxin-inducible xylem differentiation has not been fully elucidated and remains difficult to manipulate. Here, we found that an antagonist of spermidine can act as an inhibitor of thermospermine biosynthesis and results in excessive xylem differentiation, which is a phenocopy of a thermospermine-deficient mutant acaulis5 in Arabidopsis thaliana. We named this compound xylemin owing to its xylem-inducing effect. Application of a combination of xylemin and thermospermine to wild-type seedlings negates the effect of xylemin, whereas co-treatment with xylemin and a synthetic proauxin, which undergoes hydrolysis to release active auxin, has a synergistic inductive effect on xylem differentiation. Thus, xylemin may serve as a useful transformative chemical tool not only for the study of thermospermine function in various plant species but also for the control of xylem induction and woody biomass production. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 49 2008 A cross-metathesis approach to the stereocontrolled synthesis of the AB ring segment of ciguatoxin 3643 3647 EN Isao Kadota Takashi Abe Miyuki Uni Hiroyoshi Takamura Yoshinori Yamamoto <p>Synthesis of the AB ring segments of ciguatoxin is described. The present synthesis includes a Lewis acid mediated cyclization of allylstannane with aldehyde, cross-metathesis reaction introducing the side chain, and Grieco-Nishizawa dehydration on the A ring.</p> No potential conflict of interest relevant to this article was reported.