有機合成化学協会誌

生命現象の解明と制御に挑む生物有機化学

公開日: 2026/03/06 更新日: 2026/03/06

有機合成化学は、複雑な生命現象を分子レベルで解明し、制御するための鍵となる分子や手法を創り出すことで、科学の発展に大きく貢献してきました。本スポットライトでは、1991年から25年間に本誌に掲載された総合論文の中から、生物有機化学分野に関連する論文を選定しました。
基礎的な反応機構の研究から分子プローブや生物活性分子の創製に至るまで、生命科学のフロンティアを切り拓いてきた有機合成化学のアプローチの深さと広がり、そしてその変遷をご覧ください。
（編者一同）

27件中1～20件の論文を表示しています

49 巻 (1991) 8 号 p. 748-761 公開日: 2026/03/06
FK506およびFKBPプローブ試薬, (C₈, C₉-¹³C₂) -FK506の全合成
中塚正志, Stuart L. SCHREIBER

Asymmetric syntheses of FK 506 and (C₈, C₉-¹³C₂) -FK 506 are reported. The latter compound was designed to facilitate an investigation of the interactions between FK 506 and its receptor, the recently discovered immunophilin, FKBP. The synthesis involved the preparation of intermediates 7-9 in nonracemic forms. The key coupling reactions included a Cram-selective addition of the vinyl Grignard reagent derived from bromide 9 to aldehyde 8 and the addition of the lithioanion of phosphonamide 7 to aldehyde 43, followed by thermal elimination. Dithiane 44 was then hydrolyzed, and glycolic ester 6 (or 6^*) was added via an aldol reaction that allowed the introduction of ¹³C labels at C₈ and C₉. Elaboration to FK 506 proceeded via a Mukaiyama lactamization reaction and a selective deprotection/oxidation sequence, the efficiency of which was critically dependent upon the order of protecting group removal.
¹³C labeled FK 506 (2) -FKBP drug protein complex was examined by ¹³C NMR ; the experiments did not show an enzyme bound tetrahedral intermediate, but revealed a noncovalent, fully reversible interaction of the drug with its receptor.
Also delineated are the recent researches aiming at understanding the structural basis for the molecular recognition of immunosuppressants by immunophilins and the biological consequences of their interactions.
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49 巻 (1991) 11 号 p. 1070-1079 公開日: 2026/03/06
発癌プロモーターの作用機作解明への有機化学的アプローチ
入江一浩, 小清水弘一

Teleocidins are potent tumor promoters produced by actinomycetes. Simpler in structure and of higher stability than other potent tumor promoters, phorbol esters and aplysiatoxins, they are particularly useful for investigating the mechanism of tumor promotion using various synthetic teleocidin analogues. The authors found a teleocidin-producing actinomycete, Streptoverticillium blastmyceticum NA 34-17, which has a characteristic feature of producing (-) -indolactam-Val (ILV) in quantity, the fundamental structure of teleocidins. Using this micro-organism, they have synthesized various ILV derivatives, examined the structure-activity relationships and prepared new fluorescent or photolabile ILV derivatives for the receptor analysis of tumor promoters. They have also investigated the metabolism and biosynthesis of teleocidins. This review mainly deals with the structure-activity relationships of teleocidins, syntheses of fluorescent or photolabile ILV derivatives and their application on the receptor analysis of tumor promoters.
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53 巻 (1995) 1 号 p. 13-21 公開日: 2026/03/06
わらびの究極発癌物質の合成およびDNAとの反応
山田静之, 木越英夫

Synthetic studies on the bracken ultimate carcinogen (3) and its artificial analogues (32, 33) are described. The synthesis of (-) -ptaquilosin (2) the aglycon of a potent carcinogen ptaquiloside (1) from bracken and its (+) - enantiomer (ent- 2) was achieved starting with (+) -dimenthyl (1R, 2R) -cyclopentane-1, 2-dicarboxylate. Dehydration of ptaquilosin (2) under weakly basic conditions led to the ultimate carcinogen (3). DNA cleaving activities of both enantiomers (3) were compared, the one (3) derived from natural (-) -ptaquilosin (2) being more efficient. Reactivities of the ultimate carcinogen (3) toward DNA are described. DNA was shown to be alkylated at the particular sites of purine bases and to undergo cleavage. The molecular mechanism of DNA cleavage with the ultimate carcinogen (3) was disclosed using deoxytetranucleotide d (GTAC) as a model DNA substrate.
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54 巻 (1996) 7 号 p. 596-606 公開日: 2026/03/06
オワンクラゲ生物発光の分子過程
平野誉, 大橋守

The photoprotein aequorin isolated from the jellyfish Aequorea victoria emits blue light in the presence of Ca²⁺ with a high quantum yield. Aequorin consists of apoaequorin (apoprotein), coelenterazine, and molecular oxygen. Coelenterazine also has a chemiluminescent reactivity with oxygen. In vivo, the excited energy generated by aequorin is transferred to a green fluorescent protein (GFP), which emits green light after energy transfer. The molecular processes in the jellyfish bioluminescence have been studied for designing a highly efficient luminescent compound and for establishing the supramolecular interaction between coelenterazine and apoaequorin as well as the interaction between aequorin and GFP. This review describes the chemiluminescent reaction mechanism of coelenterazine, the supramolecular structure and the bioluminescent character of aequorin investigated by the use of chemically modified coelenterazines and apoaequorin mutants, and the character of GFP.
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56 巻 (1998) 7 号 p. 581-590 公開日: 2026/03/06
構造生物学的有機化学 : 光アフィニティーラベルによる蛋白質機能構造のプロービング
畑中保丸

Based on the recent development of recombinant techniques, the investigation of biofunctional machinery at their ligand accepting interfaces has become a challenging and important subject of organic chemistry in the oncoming new century. Three major approaches currently used for structural biology have their own advantages and limitations. Spectroscopic methods are useful for analyzing ligand-receptor interactions at the atomic level. These approaches, however, usually require a significant amount of stable and pure proteins. Protein engineering based on gene technologies provides a series of mutants for the structural analysis of functional sites. One prerequisite for the use of this methods is that the mutants must, to a large extent, retain the conformation of the native receptors. Photoaffinity labeling, one of the third independent approach, has become increasingly appreciated as a powerful chemical methodology for the detailed structural analysis of ligand binding domains. The technique of photoaffinity labeling is a reliable chemical method which should be considered as being complementary to, rather than in competition with, the other two approaches. This review is focusing the recent application of photoaffinity labeling for probing the functional structure of ion channels, receptors, and enzymes.
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58 巻 (2000) 8 号 p. 745-755 公開日: 2026/03/06
スクアレン環化酵素の生物有機化学
阿部郁朗

Enzymatic cyclizations of squalene and oxidosqualene lead to various skeletal types of sterols and triterpenes. The cyclases for these reactions catalyze formation and stabilization of polycyclic carbocations and direct the enzyme-specific, templated formation of new carbon-carbon bonds in regio- and stereochemically defined manner. Studies of these enzymes are now progressing rapidly and promise to reveal the intimate three-dimensional structural details of the enzyme-catalyzed processes. The development of mechanism-based irreversible inhibitors, photoactivatable inhibitors, and numerous substrate analogs have helped to unravel the stepwise events occurring in the catalytic sites of these enzymes by covalent modification of specific amino acid residues.
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62 巻 (2004) 5 号 p. 490-499 公開日: 2026/03/06
花の色とナノサイエンス
吉田久美, 尾山公一, 近藤忠雄

Red, purple and blue flower color is mainly due to anthocyanins. The color development and stability of anthocyanin are effected by co-existence of co-pigment and metal ions, and pH. Our chemical studies elucidated that the color is stabilized and varied by formation of a supramolecule. Especially beautiful blue flower colors, found in blue dayflower and blue salvia, are developed by a metalloanthocyanin, a stoichiometric supramolecular metal complex pigment.
The metalloanthocyanins are composed with six molecules of anthocyanins, six molecules of glycosylflavones, and 2 atoms of metal ion and the diameter is ca. 3 nano meter. Under formation of metalloanthocyanin fine chiral molecular recognition occurs. To clarify the mechanism we synthesized chiral glycosylflavones derivatives according to our newly invented method of direct C-and O-glycosylation to the flavonoid nucleus. Reproduction experiment from the components (anthocyanin, flavone and metal ion) including chiral isomer of the flavones bearing L-glucose was carried out. As a result, the 4'-D-glucoside of the flavone is essential for formation of metalloanthocyanin, but the L-sugar is not.
As the petal tissue is not homogenous, both the epidermides are colored. For elucidation of true flower color development in a living petal cell, various analytical methodologies including nano-technology must be applied. For this purpose one cell analysis by pH-microelectrode, a nano-HPLC, a pico mole metalanalysis and microscopic photometry were carried out. The mech-anism of flower color change of morning glory, Ipomoea tricolor, from purple to blue during blooming, and color variation of hydrangea was studied.
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62 巻 (2004) 10 号 p. 968-977 公開日: 2026/03/06
ユビキチン-プロテアソームシステムをターゲットとする天然物化学・創薬化学の新しい展開
塚本佐知子, 横沢英良

The ubiquitin-proteasome proteolytic pathway plays a major role in selective protein degradation and regulates various cellular events including cell cycle, signal transduction, stress response, antigen presentation, and protein quality control. Ubiquitin, a highly conserved small protein in eukaryotes, attaches to a target protein prior to degradation. The polyubiquitin chain tagged to the target protein is recognized by the 26 S proteasome, a high-molecular-mass protease subunit complex, and the protein portion is degraded by the proteolytic active sites in a cavity of the 26 S proteasome. The potential of specific proteasome inhibitors, which act as anti-cancer agents, is now under intensive investigation. In addition, various inhibitors of a ubiquitin-activating enzyme, ubiquitin ligases, and deubiquitinating enzymes have been isolated from natural resources. Recently, we found that girolline, an antitumor compound, inhibits the recruitment of polyubiquitinated proteins to the proteasome. In this review, we summarize the structures and biological activities of natural products that inhibit various factors involved in the ubiquitin-proteasome proteolytic pathway.
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62 巻 (2004) 10 号 p. 1006-1013 公開日: 2026/03/06
細胞機能を覗く可視化センサー分子のデザイン・合成・生物応用
菊地和也, 長野哲雄

One of the great challenges in the post-genome era is to clarify the biological significance of intracellular molecules directly in living cells. If we can visualize a molecule in action, it is possible to acquire biological information, which is unavailable if we deal with cell homogenates. One possible approach is to design and synthesize sensor molecules that can convert biological information to chemical reactions that are easily monitored. For this purpose, fluorescence sensor molecules for intracellular messengers have been developed and successfully applied to living cells.
Ratiometric measurement is a technique to reduce artifacts by minimizing the influence of extraneous factors on the fluorescence of a sensor molecule. FRET is one mechanism that is applicable for ratiometric measurement. We have designed two FRET sensor molecules, based on changing donor-acceptor distance and changing overlap integral. Protein tyrosine phosphatase activity was successfully monitored by designed sensor. Design, synthesis and neurological application of Zn²⁺ specific sensor molecules are also introduced.
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64 巻 (2006) 2 号 p. 141-150 公開日: 2026/03/06
タンパク質人工機能化と機能制御のための有機化学
王子田彰夫, 宮原芳文, 浜地格

In recent years, a variety of chemical methods for selective labeling or functional modulation of protein of interest has been developed. In this article, we focus on synthetic organic chemistry for protein modification, especially on the recent developments of the bioorthogonal reactions, which enable to hybridize an artificial small molecule to a protein of interest with a site-selective manner. On the other hand, covalent bond formation of protein with a small molecule has also been recognized as a powerful strategy to regulate protein functions, and enormous efforts have been devoted to develop selective irreversible inhibitors for proteins, especially for the families of proteases, in the research field of medicinal chemistry. We also provide an overview of the irreversible inhibitors, including their recent advancements and some applications for proteome analysis or drug discovery. In addition, we report herein our original method (P-PALM) for site-selective modification of a protein using the photo-affinity labeling technique. The utility of the P-PALM method has been successfully demonstrated in the modifications of the lectin into the new fluorescent saccharide biosensors.
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64 巻 (2006) 2 号 p. 117-129 公開日: 2026/03/06
機能性分子プローブを用いた植物就眠運動の生物有機化学
上田実, 藤井智彦, 加藤英介, 杉本貴謙, 加藤信樹

Circadian rhythmic plant leaf-movement, called nyctinasty, is controlled by a time-course change in the internal concentration of the leaf movement factors (leaf-opening and leaf-closing substances) in the plant body. We revealed that the target cell for the leaf-movement factors is plant motor cell by using novel synthetic fluorescence labeled probes. Using photoaffinity probes 21, the specific binding proteins for potassium lespedezate 1, the leaf-opening substance of Cassia mimosoides L, are detected from the plasma membrane fraction of the plant motor cell. Our study is a rare successful result of the detection of membrane receptors by using a synthetic photoaffinity probe designed on a biologicallly active natural product. These results also advance a guideline for probe design towards successful photoaffinity labeling. The balance of concentration of the leaf movement factors is inversed during the day. The glycoside type leaf movement factor is hydrolyzed with β-glucosidase, the activity of which is regulated by the biological clock. The circadian rhythm observed in the leaf movement is introduced by activation of the β-glucosidase regulated by the biological clock. We synthesized the glyconoamidine gel 43 designed on potassium lespedezate, a glycoside type leaf-opening substance, and succeeded in purification of the β-glucosidase, a key enzyme of circadian rhythmic plant leaf-movement, by affinity chromatography using affinity gel 43.
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64 巻 (2006) 5 号 p. 502-514 公開日: 2026/03/06
誘導体および同位体標識化合物を用いたアンフォテリシンBイオンチャネル構造の解明
松森信明, 大石徹, 村田道雄

Amphotericin B (AmB) is known to assemble together and form an ion channel across biomembranes. The selective toxicity is generally accounted for by its higher affinity for ergosterol than cholesterol. To better understand the ion-channel structure and intermolecular interactions, we prepared various AmB derivatives and measured their activities. AmB dimers which are covalently linked between the amino groups by short chains showed more potent ion-channel activity than that of AmB, indicating that the mutual topology of AmB molecules is a head-to-head orientation. AmB-sterol conjugates were also designed and examined for ion-channel activities. AmB-ergosterol conjugates showed more powerful ion-channel activity than AmB-cholesterol congeners, suggesting that stronger van der Waals interaction between AmB and ergosterol contributes to the higher ion-channel activity. Finally, we prepared conformation-restricted derivatives of AmB, in which the amino and carboxyl groups were bridged with various lengths of alkyl chains. The derivatives successfully gave us information on the active-conformation of the sugar moiety of AmB in membrane. These derivatives are now labeled by ¹³C and/or ¹⁹F to probe the molecular structure of AmB ion channel using solid-state NMR.
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64 巻 (2006) 5 号 p. 515-528 公開日: 2026/03/06
プロテインキナーゼC (PKC) の構造と活性化機構の解明を目指した新規C1ドメインリガンドの創製
平井剛, 清水忠, 袖岡幹子

Protein kinase C (PKC) is a family of enzymes which play important roles in intracellular signal transduction. We designed a series of novel PKC ligands having an isobenzofuranone (IB) template, based on the proposed interaction of DAG (1, 2-diacyl-sn-glycerol) with PKC. Since interaction of the hydrophobic alkyl chain of the IB derivatives with lipid membrane is expected to be critical for the PKC activation, we were interested in the synthesis of the IB derivatives having the hydrophobic alkyl chain at various positions of the benzene ring. Effects of these synthetic ligands on the PKCα phosphorylation activity were examined. Surprisingly, 4-substitued derivative showed no activation of PKCα even at high concentration at which significant binding to PKCα was observed. These results suggest that position of the hydrophobic chain is critical for the PKC activation.
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64 巻 (2006) 5 号 p. 529-538 公開日: 2026/03/06
合成化合物を起爆剤としたケミカルバイオロジー
佐藤綾人, 上杉志成

In human history, small organic molecules have been utilized for improving human health and for revealing secrets of life. Discovery or design of small organic molecules with unique biological activity permits small-molecule-initiated exploration of biology and further understanding of human diseases. Our laboratory has been discovering and designing bioactive small synthetic molecules to use them as tools to explore biology. This personal perspective summarizes our contributions to chemical biology, particularly in the fields of gene transcription, library design, and growth factor signaling.
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64 巻 (2006) 6 号 p. 639-650 公開日: 2026/03/06
ケミカルゲノミクス研究用ツールとしての低分子有機化合物のマイクロアレイ化技術
叶直樹, 長田裕之

The identification of small molecule ligands for cellular proteins of biologically importance has not only provided new insights in biology, but has also provided organic chemists with the opportunity to create new synthetic molecules which efficiently regulate specific protein-protein interactions and biological processes. Small-molecule microarrays are recently developed as platforms to screen such small molecule ligands for proteins of interest. The small-molecule microarray technology is highly dependent on chemistry to immobilize small molecules on a variety of solid surfaces, and synthetic organic chemistry will continue to play a significant role in this field. This review covers the recent advances in the field with particular emphasis on the immobilization chemistry, as well as technical advances in the platform optimization and the successful applications of this platform.
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64 巻 (2006) 12 号 p. 1251-1260 公開日: 2026/03/06
カバの赤い汗に関する化学
橋本貴美子, 犀川陽子, 中田雅也

Hippopotamus produces colorless sweat over its entire body. The color of the sweat turns red within a few minutes and then becomes brown during a few hours by producing polymers. We isolated the unstable red and orange pigments, called hipposudoric acid and norhipposudoric acid, respectively, responsible to the red coloration of the sweat. Syntheses of these pigments were performed using the Pschorr reaction for the formation of the fluorenone core and the oxidation in the last step producing the unstable diquinone as the key steps. The tautomeric structures of the common chromophore of these pigments in a protic solvent and in an aprotic solvent were also discussed.
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64 巻 (2006) 12 号 p. 1273-1281 公開日: 2026/03/06
アクチン脱重合分子の合成と活性
末永聖武, 木越英夫

Aplyronine A 1 is a potent antitumor macrolide isolated from the sea hare Aplysia kurodai. Aplyronine A interacts with actin, one of the major proteins in cytoskeleton. We achieved total synthesis of aplyronine A and its 18 analogs and investigated structure-activity relationships. Analysis of the interaction of aplyronine analogs with actin by a photoaffinity labeling method and X-ray crystal structure analysis of actin complex with aplyronine A have been carried out. These results revealed that aplyronine A binds to actin at the hydrophobic cleft between subdomains 1 and 3 of actin. The binding mode of the macrolactone part of aplyronine A was different from previously reported macrolides. In addition, the trimethylserine moiety of aplyronine A, the essential functional group for cytotoxicity against HeLa S₃ cells, was sticking out from a surface of actin-aplyro-nine A complex.
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65 巻 (2007) 12 号 p. 1170-1178 公開日: 2026/03/06
生体内の情報伝達に関わる鍵化合物の合成と機能解析
藤本ゆかり

Signal transduction systems for detection of surrounding information are the one of essential functions for life. One of these systems is the sensory system such as vision, olfactory and gustatory. The innate immune system is also fundamental to protect our body, which basically senses microbial components by receptor proteins. In order to elucidate the function of the key molecules in the signal transduction, we have studied it on the view of organic chemistry. Here, the results on the following key compounds will be shown; one is 11-cis-retinal in a light-receptor rhodopsin essential in vision, and the others are bacterial lipopolysaccharide and peptideglycan in the innate immune system.
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66 巻 (2008) 7 号 p. 683-693 公開日: 2026/03/06
植物ポリケタイド合成酵素の触媒機能の制御
阿部郁朗

Recent progress of our research on the plant-specific type III polyketide synthases (PKSs) is described. First, our studies demonstrated that the enzymes accept a variety of substrate analogues to synthesize products chemically and structurally different from the natural products. Manipulation of the enzymes by artificial substrates could thus lead to development of a chemical library of pharmaceutically important novel polyketides. Second, a growing number of functionally divergent type III PKSs have been cloned and characterized, which include recently obtained pentaketide chromone synthase and octaketide synthase from the aloe plant. Structure function analysis revealed that a chemically inert single residue lining the active-site cavity determines the polyketide chain length and the product specificity. The functional diversity of type III PKSs is thus evolved from the simple steric modulation of the active-site cavity accompanied by conservation of a Cys-His-Asn catalytic triad. These results provided novel strategies for the engineered biosynthesis of plant polyketides.
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68 巻 (2010) 5 号 p. 490-500 公開日: 2026/03/06
新規有用天然有機化合物の開拓とケミカルバイオロジー研究
掛谷秀昭, 西村慎一

Exploitation of novel small molecules from natural sources such as microbial metabolites, medicinal plants, and marine invertebrates has contributed to the discovery of lead molecules for drugs as well as research tools on chemical biology. Chemical biology based on forward/reverse chemical genetics is a new paradigm that accelerates drug development and the functional analysis of genes and proteins. Moreover, novel natural products with unique structural or biological characteristics attract both chemists and biologists, thereby developing the field of chemical biology and medicinal chemistry. We have discovered several novel bioactive microbial metabolites by both in vivo cell–based phenotypic screenings and in vitro target–oriented screenings, and investigated their modes of action using a chemical genetics or a chemical genomics approach. In this review, we focus on the following topics; i) recent screening technology and the chemical library, ii) overview of bioactive natural products and semi–synthetic derivatives we have discovered, iii) chemical genetics approach for apoptosis signaling pathway, iv) chemical genomics approach for target identification of antifungal agent, and v) perspective.
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