研究者詳細 - 坂倉　彰

Selective synthesis of phosphate monoesters by dehydrative condensation of phosphoric acid and alcohols promoted by nucleophilic bases 査読

Akira Sakakura, Mikimoto Katsukawa, Kazuaki Ishihara

Organic Letters 7 ( 10 ) 1999 - 2002 2005年5月

Molybdenum oxides as highly effective dehydrative cyclization catalysts for the synthesis of oxazolines and thiazolines 査読

Akira Sakakura, Rei Kondo, Kazuaki Ishihara

Organic Letters 7 ( 10 ) 1971 - 1974 2005年5月

Bulky diarylammonium arenesulfonates as selective esterification catalysts 査読

Kazuaki Ishihara, Shoko Nakagawa, Akira Sakakura

Journal of the American Chemical Society 127 ( 12 ) 4168 - 4169 2005年3月

Formal synthesis of optically active ingenol via ring-closing olefin metathesis 査読

Kazushi Watanabe, Yuto Suzuki, Kenta Aoki, Akira Sakakura, Kiyotake Suenaga, Hideo Kigoshi

Journal of Organic Chemistry 69 ( 23 ) 7802 - 7808 2004年11月

Spongiacysteine, a novel cysteine derivative from marine sponge Spongia sp. 査読

Keiko Kobayashi, Hiroki Shimogawa, Akira Sakakura, Toshiaki Teruya, Kiyotake Suenaga, Hideo Kigoshi

Chemistry Letters 33 ( 10 ) 1262 - 1263 2004年10月

99(P-32) 光学活性インゲノールの合成(ポスター発表の部)

渡邉和志, 鈴木佑人, 青木健太, 坂倉彰, 末永聖武, 木越英夫

天然有機化合物討論会講演要旨集 ( 46 ) 569 - 574 2004年10月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Ingenol is a diterpenoid isolated from Euphorbia ingens, possessing a bicyclo[4.4.1]undecane skeleton with a highly strained inside, outside-intrabridgehead stereochemistry. Several strategies for construction of the unique skeleton have been reported, however, direct cyclization to the inside, ousidet-bicyclo[4.4.1]undecane system has not been reported. Recently, two total syntheses in a racemic form using the aforementioned strategies were reported by Winkler and Tanino-Kuwajima. We would like to report the construction of strained carbon skeletons of ingenol by direct cyclization with ring-closing olefin metathesis (RCM). With well-designed diene compounds 4, 23, and 24, RCM was found to be applicable to the formation of a highly strained skeleton of ingenol, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of ketone 21 with an allylic chloride unit and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 17, the key intermediate aldehyde 27 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.

DOI： 10.24496/tennenyuki.46.0_569

58(P-35) 海洋産抗腫瘍性物質アプリロニンA関連化合物の合成と生物活性(ポスター発表の部)

末永聖武, 黒田武史, 半田知久, 宮沙織, 兼松憲吾, 坂倉彰, 山田靜之, 木越英夫, 平田邦生, 高田昌樹, 加藤健一, 村岡真, 山本雅貴, 田中宏志

天然有機化合物討論会講演要旨集 ( 46 ) 323 - 328 2004年10月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Aplyronine A (1) is a potent antitumor macrolide isolated from the sea hare Aplysia kurodai, and mycalolide B (2) is a cytotoxic and antifungal macrolide isolated from a sponge of the genus Mycale. These macrolides interact with actin, one of the major proteins in cytoskeleton. We achieved total synthesis of aplyronine A (1) and its analogs and investigated the structure-activity relationships. We improved the synthesis of the side chain portion of aplyronine A (1) by using the Paterson aldol reaction and subsequent stereoselective reduction with Me_4NBH(OAc)_3 as key steps. The synthetic analogs 3 and 4 that only consists of the side chain part of aplyronine A (1) and mycalolide B (2) turned out to exhibit a strong actin depolymerizing activity, considering the size of the molecule. This result revealed that the side chain portion in aplyronine A (1) and mycalolide B (2) was responsible for the potent activity of 1 and 2. Analysis of the interaction of aplyronine analogs, such as 30 and 31, with actin by a photoaffinity labeling method has been carried out. Crystallization and X-ray structure analysis of actin complex with aplyronine A (1) also are in progress.

DOI： 10.24496/tennenyuki.46.0_323

Jolkinolide D pharmacophore: Synthesis and reaction with biomolecules 査読

Akira Sakakura, Yui Takayanagi, Hiroki Shimogawa, Hideo Kigoshi

Tetrahedron 60 ( 33 ) 7067 - 7075 2004年8月

Synthesis and actin-depolymerizing activity of mycalolide analogs 査読

Kiyotake Suenaga, Saori Miya, Takeshi Kuroda, Tomohisa Handa, Kengo Kanematsu, Akira Sakakura, Hideo Kigoshi

Tetrahedron Letters 45 ( 28 ) 5383 - 5386 2004年7月

Nonspecificity Induces Chiral Specificity in the Folding Transition of Giant DNA 査読

Michiko Ito, Akira Sakakura, Naomi Miyazawa, Shizuaki Murata, Kenichi Yoshikawa

Journal of the American Chemical Society 125 ( 42 ) 12714 - 12715 2003年10月

106(P-60) ジョルキノライドDファーマコホア : 合成とアミノ酸、ヌクレオシドおよびDNAに対する反応性(ポスター発表の部)

坂倉彰, 高柳維, 下川浩輝, 木越英夫

天然有機化合物討論会講演要旨集 ( 44 ) 623 - 628 2002年9月

記述言語：日本語出版者・発行元：天然有機化合物討論会

Jolkinolide D (1) is a diterpenoid isolated from Euphorbia jolkini Boiss in 1974, and its stereostructure was recently determined by X-ray crystallographic analysis. It inhibited tumor invasion into the basement membrane and induced apoptosis in tumor cells. Jolkinolide D (1) has a γ,δ-unsaturated-β-hydroxy-α-methylene lactone unit as the pharmacophore structure, which suggests that jolkinolide D (1) might alkylate biomolecules such as proteins and DNA irreversibly. Since there are no other compounds that have the pharmacophore, reactivities of the unit toward nucleophiles have not hitherto been investigated. For the purpose of obtaining preliminary information on the chemical modification of biomolecules with jolkinolide D (1), jolkinolide D pharmacophore (2) was synthesized from 6-(tert-butyldimethylsilyloxy)-3-methyl-2-cyclohexenone (3) and 2-iodoallylalcohol (4), and its reactivity toward amino acids, nucleosides, and DNA was investigated. It was found that the order of reactivity of jolkinolide D pharmacophore (2) toward the nucleophiles in the amino acids at pH 7.5 is the thiol group in L-cysteine and glutathione > the imidazolyl group in L-histidine, the α-amino groups in amino acids > the carboxyl groups in amino acids. Jolkinolide D pharmacophore (2) alkylated 2'-deoxyguanosine at the N-1 position (pH 7.5) and thymidine at the N-3 position (pH 8.7), and modified DNA at the same sites in lower yields.

DOI： 10.24496/tennenyuki.44.0_623