Biological and Organic Chemical Investigation on Blepharismins and Their Related Natural Products

眼睑素及其相关天然产物的生物和有机化学研究

• 批准号: 10480151
• 负责人: KOTSUKI Hiyoshizo
• 金额: $ 8.38万
• 依托单位: Kochi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10480151/
• 关键词: Blepharismins; Aromatic Alkylation; Anthraquinone Structures; Oxidative Coupling; Photosignaling; Stentorins; Hypericin; Photosensory Transduction; アントラキノン; ヒペリミン; Friedel-Craftsアルキル化; アントロン; 光シグナル; 光センサー複合体; Sc(OTf)3; 分子内Friedel-Craftsアシル化

(a) Structural Study of Blepharismins and Their Related Natural Pigments : Computer-aided analysis of blepharismins, stentorins, and hypericin has been performed and their three-dimensional structures having the "propeller" butterfly-like conformation have been clarified.(b) Synthetic Study of Blepharismins and Their Related Natural Pigments :-1. New Method for Aromatic Alkylation : To introduce an alkyl side chain on an aromatic ring, we developed the following two methods : (a) Friedel-Crfats-type alkylation using secondary alcohol methanesulfonates as an electrophile in the presence of a catalytic amount of Sc(OTf)_3 or TfOH ; (b) Regioselective nucleophilic aromatic substitution using Grignard reagents upon o- or p-methoxy-substituted aromatic carboxylates.-2. Synthesis of Anthraquinone Key Skeletons : The anthraquinone key component of blepharismin-3 and stentorin-C was prepared by treatment of benzoic acid derivatives with (CF_3CO)_2O via intramolecular Friedel-Crafts acylation f … More ollowed by oxidation in the air.-3. High-Pressure Promoted Construction of Biphenol Key Skeleton : High-pressure promoted condensation between phenols and aromatic aldehydes was efficiently proceeded in the presence of a catalytic amount of TfOH to produce the desired biphenol key skeleton of blepharismins.-4. Synthesis of Perylene Quinone Structure : Intramolecular oxidative coupling of biphenol derivatives has been achieved by using the Koga' reagent (CuCl(OH)・TMEDA complex) in giving the perilene quinone structure of blepharismins.(c) Structure of Photosensory Complex : Spectroscopic analysis of free pigment(blepharismin) and pigment (blepharismin)/protein complex, analysis of pigment contents bound to the protein or observation of photosensory organelle suggested that a large number of free pigment molecules are regularly arranged in vivo. This crystal -like structure may function as light-harvesting antenna for activating reaction center blepharismin/200 kD proteincomplex.(d) Photosensory Transduction : Analyses of molecular structure of light-irradiated blepharismin suggested that light-induced dissociation of phenol group (side chain) is notinvolved in activation of photosensory transduction chain. Spectroscopic analysis of photoreceptor complex indicated that active oxygen produced by photosensitization of light-activated blepharismin or energy or electron transfer from first excited singlet of pigment would be involved in activation of photosensory transduction chain.(e) Singaling Mechanism between Photoreceptor Organelle and Cell Membrane : We revealed that photosignal is finally transduced into H+ signal ; H+ is released from outer membrane of photoreceptor organelle so that evoked depolarization of cell membrane. Less

(a)Blepharismins及其相关天然色素的结构研究：对Blepharismins、stentorins和金丝桃素进行了计算机辅助分析，并阐明了它们具有“螺旋桨”蝴蝶状构象的三维结构。(b)Blepharismins及其相关天然色素的合成研究：-1。芳族烷基化的新方法：为了在芳环上引入烷基侧链，我们发展了以下两种方法：（a）在催化量的Sc（OTf）_3或TfOH存在下，以仲醇甲磺酸盐为亲电试剂的Friedel-Crfats型烷基化;（B）在邻或对甲氧基取代的芳族羧酸盐上使用Grignard试剂的区域选择性亲核芳族取代。2.蒽醌类关键化合物的合成：以苯甲酸衍生物为原料，经（CF_3CO）_2O分子内Friedel-Crafts酰基化反应，合成了蒽醌类关键化合物blepharismin-3和stentorin-C。 ...更多信息 在空气中被氧化3.高压促进的双酚关键骨架的构建：在催化量的TfOH存在下有效地进行酚和芳族醛之间的高压促进的缩合，以产生所需的小泡菌素的双酚关键骨架。4.紫苏醌结构的合成：利用古贺试剂（CuCl（OH）·TMEDA络合物）实现了双酚衍生物的分子内氧化偶联，得到了紫苏醌结构。(c)感光复合体的结构：游离色素（blepharismin）和色素（blepharismin）/蛋白质复合体的光谱分析，结合蛋白质的色素含量分析或感光细胞器的观察表明，大量游离色素分子在体内有规律地排列。这种晶体状结构可能作为捕光天线激活反应中心blepharismin/200 kD蛋白复合物。(d)感光转导：对光照射后的小睑球蛋白分子结构的分析表明，光诱导的侧链酚基解离不参与光敏转导链的激活。光感受器复合体的光谱分析表明，光激活的眼睑色素光敏化产生的活性氧或色素第一激发单态的能量或电子转移可能参与光敏转导链的激活。(e)光感受器细胞器与细胞膜之间的信号传递机制：光信号最终转化为H+信号，H+从光感受器细胞器外膜释放，引起细胞膜去极化。少

项目成果

K.Gamoh: "Catalytic Activity and Enantioselectivity in Organic Solvent of Lipase Immobilized on ODS-sugar Ester"BUNSEKIKAGAKU. 48. 1149-1155 (1999)

K.Gamoh：“固定在 ODS-糖酯上的脂肪酶在有机溶剂中的催化活性和对映选择性”BUNSEKIKAGAKU。

蒲生啓司,坂田知栄子,小槻日吉三: "ODS-ショ糖エステルに固定化したリパーゼの有機溶媒中での酵素活性およびエナンチオ選択性"分析化学. 48. 1149-1155 (1999)

Keiji Gamo、Chieko Sakata、Hikizo Otsuki：“有机溶剂中固定在 ODS-蔗糖酯上的脂肪酶的酶活性和对映选择性”分析化学 48. 1149-1155 (1999)。

T.Matsuoka: "Photosensory Transduction in Unicellular Eukaryote Blepharisma"J.Exp. Zool.. (in press)..

T.Matsuoka：“单细胞真核生物 Blepharisma 中的光传感转导”J.Exp。

T.Kojima 他4名: "A New Practical Method for Regioselective Nucleophilic Aromatic Alkylation of ortho-or para-Methoxy substituted Aromatic・・・・"Tetrahedron Letters. 42. 1709-1712 (2001)

T. Kojima 和其他 4 人：“邻位或对位甲氧基取代的芳族化合物的区域选择性亲核芳族烷基化的新实用方法......”四面体快报 42. 1709-1712 (2001)。

T.Shinohara 他2名: "Asymmetric baeyer-villiger oxidation of cyclobutanones using diethylzinc / oxygen / chiral amino alcohols"Heterocycles. 55. 237-242 (2001)

T.Shinohara 和其他 2 人：“使用二乙基锌/氧/手性氨基醇对环丁酮进行不对称拜尔-维利格氧化”杂环。