著者
松尾 貴史
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.79, no.4, pp.311-321, 2021-04-01 (Released:2021-04-07)
参考文献数
49

Hoveyda-Grubbs-type complexes with a ruthenium center coordinated by an N-heterocyclic carbene (NHC) and a 2-alkoxybenzylidene ligands have gained increased applicative importance as catalysts for olefin metathesis because the complexes have suitable reactivities and stabilities in a wide range of reaction media. Furthermore, this type of catalysts has also been applied for biochemical research projects including the construction of artificial biocatalysts and the regulation of in-cell bioreactions because the ruthenium-olefin interaction, a driving force of olefin metathesis mediated by Hoveyda-Grubbs-type complexes, provides the specificity among functional groups in biomolecules. In this context, we have investigated the structural modification of Hoveyda-Grubbs-type complexes aiming at the application of the complexes to biomolecules. In parallel, we have also studied the mechanism of olefin metathesis in aqueous media. In this article, we firstly describe the construction of an artificial metalloenzyme with olefin metathesis activity using α-chymotrypsin. The artificial metalloenzyme displayed the substrate specificity with the protein surface charge state. Next, we demonstrate the importance of chloride anion in solutions to attain efficient olefin metathesis reactions in aqueous media and the reactivity control of Hoveyda-Grubbs-type complexes through second-coordination sphere effect. Finally, we introduce the ruthenium complex transfer reaction between Hoveyda-Grubbs-type complexes and biomolecules (peptides and proteins) through the ruthenium-olefin specific interaction. The reaction potentially serves a new type of chemical modification strategy toward biomolecules.
著者
中村 斐有 安井 孝介 Phil S. Baran
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.79, no.4, pp.333-343, 2021-04-01 (Released:2021-04-07)
参考文献数
32

Teleocidine B family was isolated in1960 by Sakai group and was shown to have highly potent protein kinase-C (PKC) activation, similar to that of phorbol and related natural products. In this report, we have developed a unified total synthesis of teleocidins B-1-B-4 in 11 chemical steps. The highlights of the work are 1) the Ni catalyzed electrochemical amination, 2) Cu-mediated aziridine opening followed by direct macrolactamization, and 3) the tactical combination of C-H borylation and a redox-relay chain walking (RRCW) methodology to make the carbon quaternary center.
著者
小西 彬仁 安田 誠
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.79, no.3, pp.224-233, 2021-03-01 (Released:2021-03-10)
参考文献数
46

Nonalternant hydrocarbons, which involve odd-membered rings, are an intriguing family for investigations of the structure-property relationship of π-conjugated carbocycles. Bicyclic nonalternant hydrocarbons, azulene, pentalene and heptalene, are the most fundamental molecules in a series of nonalternant hydrocarbons. Over the last 15 years, the chemistry of nonalternant hydrocarbons has experienced a remarkable renaissance mainly thanks to advances in synthetic methodologies. Ring-annulated nonalternant π-systems, in which some benzenoid rings are attached into the nonalternant frameworks, are the key players in their resurgence. The ring annulation impacts the electronic structures of nonalternant subunits, which modulates the HOMO-LUMO gap and creates perturbations in their inherent (anti)aromatic nature. The tunable, narrow HOMO-LUMO gap has offered rich studies into the electronic properties of open-shell characters and into their potential applications as functional organic optoelectronic materials. This article describes our recent studies on the synthesis and characterization of π-extended nonalternant hydrocarbons, containing azulene, pentalene and heptalene frameworks.
著者
長澤 和夫
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.79, no.1, pp.43-53, 2021-01-01 (Released:2021-01-09)
参考文献数
31

This review deals with our synthetic efforts for guanidine alkaloid of saxitoxin (STX), a paralytic shellfish toxin. STX shows potent inhibitory activity against voltage-gated sodium channels (NaVs), which are membrane proteins that involve in the generation and propagation of action potentials in neurons. More than 50 analogs of STX have been isolated from nature, and these analogs commonly possess characteristic tricyclic core skeleton including two kinds of 5-memberd and 6-memberd cyclic guanidine. For the synthesis of the core structure, we have developed a neighboring acyl group assisted cyclization strategy to give tricycle with a fully protected form of saxitoxinol under quite mild conditions. This key intermediate allows us total synthesis of (+)-decarbamoyl saxitoxin (dcSTX), (+)-gonyautoxin 3 (GTX3) including and STX. Besides, we have achieved the synthesis of 11-saxitoxinethanoic acid (SEA), which is an unusual STX derivative bearing carbon-carbon bond at the C11 position by applying Mukaiyama aldol condensation reaction with silyl enolether derived from the key intermediate of fully protected saxitoxinol. NaV inhibitory activities of some synthetic derivatives with C11-substituents in STX were also described.
著者
及川 雅人 塚本 俊太郎 諸熊 賢治 入江 樂 生駒 実
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.78, no.4, pp.292-303, 2020-04-01 (Released:2020-04-08)
参考文献数
70
被引用文献数
1

By a hybrid design of naturally derived excitatory amino acids, dysiherbaines and kainic acid, we have successfully developed a series of artificial glutamate analogs with sp3-rich scaffold via domino Ugi/Diels-Alder reaction, and domino metathesis reaction of oxanorbornenes as key steps. All of the first-generation analogs were found to be neuronally active upon mice intracerebroventricular injection. As the second-generation analogs, we then synthetically modified the heterotricyclic structure, and found that analogs with a carbonyl group on the A-ring still keep the original activity of the first-generation analogs. Structural modification of the second-generation analogs by diversity-oriented reactions such as multicomponent Prins-Ritter reaction was furthermore studied to improve the activity profiles. Electrophysiological studies have identified IKM-159 of the second-generation analogs as an antagonist selective to AMPA-type ionotropic glutamate receptor. The molecular interactions were clarified from crystallographic studies of IKM-159 in complex with GluA2 ligand-binding domain (LBD). From the structure-activity relationships and the structural insights of the complex, a new structural design is proposed herein for neuronally active agents with improved potency and selectivity. We also propose here that generation of sp3-rich scaffold by hybrid strategy of known bioactive molecules would be of use for discovery of artificial bioactive agents with novel activity profiles.
著者
安倍 学
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.77, no.5, pp.503-511, 2019-05-01 (Released:2019-05-13)
参考文献数
36

Localized singlet diradicals are key intermediates in bond-homolyses. Thorough studies of the reactive species are essential to clarify the mechanisms of the homolytic bond-cleavage and -formation processes. In general, the singlet diradicals are quite short-lived due to the fast radical-radical coupling reactions. The short-lived characteristic has retarded the thorough study on bond-homolyses. In the last two decades, the author and his research group have enjoyed conducting fundamental studies of generating spectroscopically detectable singlet diradicals to clarify the chemistry of localized singlet diradicals. Recently, a new series of long-lived singlet diradicals, viz. 1,2-diazacyclopentane-3,5-diyl and singlet diradical having macrocyclic structures, have been identified, and their electronic structures and novel reactivities were thoroughly studied using laser-flash photolysis (LFP), product analysis, emission analyses, and computational studies. During the research study, two new concepts in chemistry have emerged; (1) π-single bonding (C-π-C) and (2) the third isomer in bond-homolysis processes, i.e. puckered singlet diradicals. This article describes first a short history of localized diradicals, then, the nitrogen-atom effect on the reactivity of singlet diradicals, the chemistry of π-single bonded species, the stereoselectivity in the photochemical denitrogenation reactions, and the adiabatic bond-homolysis process in the electronically excited states.
著者
上田 将史
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.77, no.7, pp.718-719, 2019-07-01 (Released:2019-07-08)
参考文献数
9

Diarylsulfides are an important class of natural products, pharmaceutical, and functionalized molecules in various research fields such as biology, pharmacy, and material science. However, C-S bond formation reaction is often required high-temperature condition using transition metal catalysts. The appropriate substrate scope is also limited. Therefore, the development of sustainable and efficient procedures for the C-S bond formation is essential in synthetic chemistry. Herein, novel methods for the C-S coupling reaction of diarylsulfides are introduced.
著者
彦根 悠人 長友 優典 井上 将行
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.81, no.12, pp.1136-1149, 2023-12-01 (Released:2023-12-13)
参考文献数
95

Resiniferatoxin (1) belongs to a daphnane diterpenoid family, and has strong agonistic effects on TRPV1, a transducer of noxious temperature and chemical stimuli. The densely oxygenated trans-fused 5/7/6-tricarbocycle (ABC-ring) of 1 presents a daunting challenge for chemical synthesis. We accomplished three radical-based total syntheses of 1 to streamline the overall route. In the first-generation synthesis, we implemented a novel radical three-component coupling reaction. This transformation formed the hindered linkage between the A and C-rings and extended the carbon chain in a stereoselective fashion. The 7-membered B-ring was cyclized by the second radical reaction. In the second-generation synthesis, we improved the efficacy and practicality by reorganizing the reaction sequence and retaining the intermediates of the first route. Thus, we utilized intermolecular radical allylation, Stille coupling, and photocatalytic decarboxylative radical cyclization as the three key transformations. In the third-generation synthesis, we designed a specific intermediate based on the common substructure of not only 1, but also structurally related diterpenoids, and established a unified strategy. The common intermediate was efficiently built by exploiting the bridgehead radical cyclization and derivatized into 1 through efficient C-ring functionalizations. These three total syntheses of 1 together demonstrate the advantages of radical reactions for linking hindered bonds within carbocycles without damaging preexisting functionalities, thereby offering a new strategic design for multi-step target-oriented synthesis.
著者
小林 祐輔 竹本 佳司
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.81, no.5, pp.483-491, 2023-05-01 (Released:2023-05-10)
参考文献数
51

In recent years, halogen bonding (XB) interaction has attracted much attention in organic synthesis, especially for the activation of substrates. On the other hand, the use of XB interaction for the “stabilization” of molecules has been less explored. In this manuscript, the authors described our recent work on the development of new class of N-acyliminoiodinanes and iodonium ylides, which can be used as nitrene and carbene equivalents, respectively. The intramolecular XB interactions were confirmed by X-ray structure and natural bond orbital (NBO) analyses. The synthesized N-acyliminoiodinanes were found to be activated by photo-irradiation to react with silyl enol ethers, glycals, alkynes, and(hetero)aromatic compounds to afford the corresponding aminated adducts. In addition, the iodonium ylides baring intramolecular XB interaction underwent additive-free chemoselective coupling reaction of thioamides, even in protic polar solvents. The intramolecular XB could also control the coordination mode of the nucleophile via σ-holes, suppressing undesired side reactions. These findings would pave new avenues chemoselective coupling reactions using hypervalent iodine compounds.
著者
奥田 靖浩
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.80, no.3, pp.246-247, 2022-03-01 (Released:2022-03-09)
参考文献数
8

As the mesityl group-substituted acridinium photocatalyst has an orthogonal structure, the π-systems are not conjugated, leading to the formation of a long-lived electron-transfer state depicted as Acr•-Mes•+ under photoirradiation conditions. Since this excited acridinium salt displayed a strong oxidizing ability (E*1/2=+2.06 V vs. SCE), single-electron oxidation of alkenes and arenes was accomplished. Applying this arene oxidation as key radical initiation protocol, direct C-H amination, cyanation, fluorination of electron-rich arenes and desulfurative [4+2] benzannulation were developed. Moreover, a single-electron reduced TICT state served as photoreductant in reductive dehalogenation of aryl halides and detosylation of N-tosylamines.
著者
芝 哲夫
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.48, no.8, pp.758-763, 1990-08-01 (Released:2009-11-13)
参考文献数
26

わが国の明治時代の化学者たちの生き様には現代の我々が研究を進めるに当って参考になり学ぶことが多い。鈴木梅太郎のビタミンB1の発見, 下瀬雅允と下瀬火薬, Bälzの言葉, 高峰譲吉のタカジアスターゼおよびアドレナリンの発見の物語を紹介して私見を加える。
著者
百合野 大雅 大熊 毅
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.81, no.3, pp.235-243, 2023-03-01 (Released:2023-03-07)
参考文献数
66

Isonitrile (R-NC) is a regioisomer of the corresponding nitrile (R-CN), whose C-terminus has carbene like property. Isonitriles have been deeply investigated from the viewpoint of their use. In contrast to the usability, the synthesis of isonitriles themselves are not sufficiently studied. In this manuscript, we describe our findings on catalytic nucleophilic isocyanation using cyanide with precise control of the ambident reactivity. We successfully demonstrated Pd-catalyzed allylic isocyanation. A wide variety of allylic isonitriles were obtained by this method, in high yield with good linear selectivity. Allylic nitriles were not observed at all, which were the possible side products in the reaction. Even though the reaction is the Pd-catalyzed allylic substitution, no π-allyl Pd(II) intermediate is involved in the catalytic cycle. Pd salt, such as Pd(OAc)2 and Pd(CN)2, was just the precursor of catalytic active species. It was reversibly converted into the ate complex, (Me3Si)[Pd-(CN)3], with excess amount of trimethylsilyl cyanide (Me3SiCN). The ate complex plays dual roles: 1) The Me3Si group activates phosphate leaving group on the allylation electrophile. 2) The [Pd(CN)3]- part reacts as the nucleophile with its N-terminus because the strong interaction between Pd center and C-terminus of cyanide suppresses the C-nucleophilicity. Benzylic isocyanation was successfully catalyzed by Ag2O. Both primary and secondary benzylic isonitriles were obtained in high yield. Pd-catalyzed synthesis of α-aryl-α-isocyanoacetamide derivative was also demonstrated. This catalytic procedure was appropriate to the sequential transformation into the trisubstituted oxazole without isolation of the isonitrile intermediate. Mechanistic investigations revealed that the nucleophilic isocyanation proceeded through a SN1-type substitution predominantly.
著者
菅又 功 白井 昭宏 箕浦 真生
出版者
公益社団法人 有機合成化学協会
雑誌
有機合成化学協会誌 (ISSN:00379980)
巻号頁・発行日
vol.81, no.1, pp.46-52, 2023-01-01 (Released:2023-01-10)
参考文献数
22

Gas storage and separation are closely related to various aspects of human society, such as the alleviation of greenhouse effect, promoting clean energy, and controlling harmful gases. In particular, hydrogen has been enthusiastically researched as a clean energy source that emits no greenhouse gases. Therefore, there are requirements for safe methods to manufacture, store, and transport hydrogen. Conventionally, hydrogen storage materials are metal hydrides and metal amides that react violently with moisture, and their usage environments are limited by the extreme conditions required for hydrogen gas generation. Metal-organic frameworks (PCP/MOFs) are porous coordination materials that are composed of organic ligands and metal ions. Because of their ability to efficiently adsorb small molecules, PCP/MOFs have potential applications in e.g., gas adsorption, catalysis, as well as energy storage and conversion. Functionalization and modification of the organic ligands to construct new MOFs are fascinating and significant areas in crystal engineering owing to the potential applications of the resulting materials. We describe the synthesis and gas-adsorption properties of novel MOFs using the functionalized organic ligands.