研究者業績

北島 満里子

キタジマ マリコ  (Mariko Kitajima)

基本情報

所属
千葉大学 大学院薬学研究院 准教授
学位
博士(薬学)(千葉大学)

J-GLOBAL ID
200901059580656008
researchmap会員ID
1000191975

外部リンク

受賞

 3

論文

 273
  • Daiki Hiruma, Akiho Yoshidome, Kenta Rakumitsu, Mariko Kitajima, Yuki Hitora, Sachiko Tsukamoto, Johann Schinnerl, Lothar Brecker, Hayato Ishikawa
    Chemistry – A European Journal 2025年3月2日  
    Abstract Alstrostine A and isoalstrostine A are monoterpenoid indole alkaloid glycosides with unique structures found in the plant families Apocynaceae and Rubiaceae. With molecular weights exceeding 900, nine chiral centers (excluding sugar rings), and complex fused‐ring structures, the structural elucidation of these molecules using spectral analysis is highly challenging. Therefore, their structural identification through total synthesis is important in both natural product chemistry and synthetic organic chemistry. In this study, we successfully accomplished the first asymmetric total syntheses of these alkaloids in 18 or 19 steps. A key synthetic feature was a two‐ or three‐component coupling reaction between secologanin and a pyrrolidinoindoline moiety based on our proposed biosynthetic pathway. This approach enabled the synthesis of all isomers of the pyrrolidinoindoline ring, which constitutes the upper fragment of the alstrostines, and allowed us to revise the stereochemistry of alstrostine A. Additionally, a compound previously isolated as alstrostine A from Palicourea luxurians (Rubiaceae) was successfully reidentified and renamed as epialstrostine A.
  • Kyosuke Yamanishi, Gin Ashihara, Shinya Shiomi, Shingo Harada, Mariko Kitajima, Hiromitsu Takayama, Hayato Ishikawa
    Journal of the American Chemical Society 146(39) 27152-27160 2024年9月18日  査読有り
  • Go Yoshimura, Jukiya Sakamoto, Mariko Kitajima, Hayato Ishikawa
    e202401153 2024年4月7日  査読有り
  • Sho Imaoka, Yuta Nakashima, Mariko Kitajima, Hayato Ishikawa
    Chemical & Pharmaceutical Bulletin 72(1) 68-74 2024年  査読有り
    The first enantioselective total synthesis of kopsiyunnanine B, which has a unique folded and complex pentacyclic structure containing six contiguous chiral centers, has been achieved along our originally proposed biosynthetic pathway. The key reaction of this synthesis includes a bioinspired cascade that builds three ring structures and three chiral centers in one step and features the stereoselective reduction of a β-acrylate and oxidation to an oxindole.
  • Yoshihiro Ataka, Mariko Kitajima, Hayato Ishikawa
    Organic Letters 25(42) 7601-7605 2023年10月27日  査読有り
    The enantioselective total syntheses of (-)-silicine and (-)-20-episilicine, which contain a chiral piperidine with three contiguous chiral centers (D-ring) and a strained seven-membered ring (C-ring) attached to an indole, were achieved. The key steps of these syntheses included a chiral secondary amine-catalyzed formal aza-[3 + 3] cycloaddition reaction and Lewis acid-mediated irreversible ring-closing reaction. In addition, the stereochemistry at C20 was controlled at a later stage in the syntheses.

MISC

 6

書籍等出版物

 8

講演・口頭発表等

 211
  • 鈴木悠太, 小暮紀行, 北島満里子, 高山廣光
    日本薬学会 2011年3月31日
  • 中山淳, 小暮紀行, 北島満里子, 高山廣光
    日本薬学会第131年会 2011年3月31日
  • 原田真也, 小暮紀行, 北島満里子, 高山廣光
    日本薬学会第131年会 2011年3月31日
  • 堀内保宏, 小暮紀行, 北島満里子, 高山廣光
    日本薬学会第131年会 2011年3月31日
  • 田島麻里, 小暮紀行, 北島満里子, 高山廣光
    日本薬学会第131年会 2011年3月31日
  • Mario A. Tan, 小暮紀行, 北島満里子, Maribel G. Nonato, 高山廣光
    日本薬学会第131年会 2011年3月30日
  • 木村真也, 小暮紀行, 北島満里子, 高山廣光
    日本薬学会第131年会 2011年3月29日
  • 秋山雅紀, 小暮紀行, 北島満里子, 高山廣光
    日本薬学会第131年会 2011年3月29日
  • 八十歩直子, 北島満里子, 小暮紀行, 宍戸祐之, 松崎健, 長岡正人, 高山廣光
    日本薬学会第131年会 2011年3月29日
  • 片川 和明, 北島 満里子, 相見 則郎, 高山 廣光, 原山 尚
    天然有機化合物討論会講演要旨集 2004年10月1日 天然有機化合物討論会
    The genus Lycopodium (Lycopodiaceae), which produces a potential therapeutic agent, huperzine A (1), for the treatment of Alzheimer 's disease, has been extensively studied in recent years, resulting in the isolation of a number of new alkaloids. We also succeeded in the isolation of several new alkaloids from the crude basic fraction of Lycopodium serratum Thunb. collected at Chiba prefecture. The structures of new alkaloids were elucidated by spectroscopic analyses and chemical correlations, as follows. A new alkaloid, lycoposerramine-A (2), was obtained as colorless needles (mp. 169-171℃, C_<18>H_<29>N_3O_2). The one- and two-dimensional NMR data enabled us to construct the basic skeleton of 2 possessing a fused tricyclic ring system with five- and six-membered cycloalkanes and a 1-azacyclononane, which retains the fundamental backbone of the known alkaloid, fawcettimine (3). The structure was finally established by X-ray crystallographic analysis. Lycoposerramine-A (2) is the first example of a natural product that contains a 1,2,4-oxadiazolidine-5-one residue in the molecule. The structure of second new alkaloid, lycoposerramine-B (4), was initially elucidated by spectroscopic data including the J-resolved HMBC spectra. The novel structure having a oxime function was confirmed by chemical transformation from a known alkaloid, serratinine (5), via an eight-steps operation, which included a reductive ring-opening of an α-immonium ketone group and a regioselective oximation as the key reactions. Lycoposerramine-C (14) was obtained as colorless prisms (mp. 164-165℃) and its structure possessing the fawcettimine-skeleton was determined by spectroscopic and X-ray analyses. It was found that treatment of 14 with NaOMe in MeOH afforded two known alkaloids, phlegmariurines A (15) and B (16). Other fawcettimine-related new alkaloids (20, 22-26) were isolated and these structures were inferred by spectroscopic analyses and/or chemical transformations. The biogenetic route of these new fawcettimine-related alkaloids starting from fawcettimine (3) was proposed. Ten new alkaloids (27, 29-37) having lycopodine-related structure were also isolated and their structures were elucidated on the basis of spectroscopic analyses and/or chemical transformations.
  • 高山 廣光, 藤原 里佳, 河西 寧子, 清水 寿一, 佐田 裕之, 北島 満里子, 相見 則郎
    天然有機化合物討論会講演要旨集 2002年9月1日 天然有機化合物討論会
    A number of indole and oxindole alkaloids have been isolated from the Uncaria plants (Rubiaceae) and found to possess pharmacologically significant activities. The chemical investigation of Uncaria attenuata Korth in Thailand was first carried out by UK-Thai researchers, resulting in the isolation of many Corynanthe- and heteroyohimbine-type indole and oxindole alkaloids. By the chemical re-investigation of this plant, we found novel types of oxindole alkaloids, i.e., Us-7 (1), Us-8 (2), and Us-9 (3a, 3b). Their structures have been deduced based on spectroscopic analysis and biogenetic speculation. In order to elucidate the structures unambiguously, we carried out the synthesis of these alkaloids. I. Based on the biogenetic speculation, Us-7 (1) and -8 (2), D-seco Corynanthe-type oxindole alkaloids, would be formed from normal corynanthe-type compounds through an oxidative cleavage at the enamine double bond at the C_<20>-C_<21> positions. According to this hypothesis, the stereochemistry at the C15 is most likely to be R. To elucidate the structures including the absolute stereochemistry at C15, we planned the asymmetric total synthesis of Us-7 (1) and -8 (2). Starting from (S)-glycidol (4), a chiral (R)-γ-butenolide (10) was prepared via 7 steps reactions, which was then converted to a key intermediate (14), corresponding to the monoterpenoid part of the target molecules, through a stereoselective addition of a malonate derivative (11) to the butenolide (10). Condensation of 14 with tryptamine (15) gave the lactam (16), which was transformed to the tetrahydro-β-carboline derivatives (20a, 20b) via Bischler-Napieralski reaction and N_b-formylation. The structure of 20a was determined by X-ray crystallographic analysis. The thus obtained indoles were respectively converted to oxindole derivatives. Their stereochemistry at C7 was elucidated by the comparison of CD spectra as well as NOE experiments. The final stage, i.e., hydrolysis of the acetyl ester at C20 and oxidation of the resulting secondary hydroxy group leading to Us-7 (1) and -8 (2), is in progress. II. Us-9 (3a, 3b) was deduced to be 3-oxo-7-hydroxy-3,7-secorhynchophylline by spectroscopic analysis. Based on the biogenetic speculation, Us-9 was prepared from isorhynchophylline via modified Polonovski reaction of its N-oxide and then the introduction of a hydroxy group at the C7. Two diastereomers ascribable to C7 of the natural and semi-synthetic (3a, 3b) were separated by chiral column chromatography. The absolute configulation at C7 was elucidated by comparison of the CD spectra with those of the known oxytryptophan derivatives (28a, 28b), which were prepared from L-tryptophan by Labroo's procedure.

所属学協会

 2

共同研究・競争的資金等の研究課題

 25