Design and synthesis of 2-phenyl-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-ones as potential anticancer agents starting from cytotoxic spiromamakone A

被引：16

作者：

Fuse, Shinichiro ^{[1
]}

Inaba, Kennichi ^{[2
]}

Takagi, Motoki ^{[2
]}

Tanaka, Masahiro ^{[2
]}

Hirokawa, Takatsugu ^{[3
]}

Johmoto, Kohei ^{[4
]}

Uekusa, Hidehiro ^{[4
]}

Shin-Ya, Kazuo

Takahashi, Takashi ^{[1
,5
]}

Doi, Takayuki ^{[6
]}

机构：

[1] Tokyo Inst Technol, Dept Appl Chem, Meguro Ku, Tokyo 1528552, Japan

[2] JBIC, BIRC, Koto Ku, Tokyo 1350064, Japan

[3] Natl Inst Adv Ind Sci & Technol, CBRC, Koto Ku, Tokyo 1350064, Japan

[4] Tokyo Inst Technol, Dept Chem & Mat Sci, Meguro Ku, Tokyo 1528552, Japan

[5] Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, Tokyo 1350064, Japan

[6] Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi 9808578, Japan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 66卷

关键词：

Spiromamakone A; Spiropreussione B; Spirocycle; Spiroacetal; Anticancer agent; ORIENTED-SYNTHESIS; HALIDES;

D O I：

10.1016/j.ejmech.2013.05.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The spirocycle is a key structure found in many bioactive compounds. From the cytotoxic and spirocyclic natural product, spiromamakone A (1) and its analogues, a more synthetically accessible spiroacetal template 4 was designed based on structural similarity analysis. A total of 50 compounds were rapidly synthesized in only one or two synthetic steps from the starting compound, and their cytotoxicity was evaluated. As a result, (+/-)-(2R*,5R*)-2-(4-iodophenyl)-7-chloro-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-one (7d-II) was discovered and found to be fifteen-fold more cytotoxic than 1. The easily accessible spiroacetal 7d-II appeared to act in a manner similar to the highly oxidized natural product, spiromamakone A (1). (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：180 / 184

页数：5

共 17 条

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[2] Cascade Radical 1,6-Addition/Cyclization of para-Quinone Methides: Leading to Spiro[4.5]deca-6,9-dien-8-ones
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[3] Design, Synthesis, and Antitumor Activity of a Series of Novel 4-(Aromatic Sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-ones
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[4] Synthesis of 1-Substituted 2-Azaspiro[4.5]deca-6,9-dien-8-ones and 2-Azaspiro[4.5]deca-1,6,9-trien-8-ones by Condensation of 2,6-Dimethylphenol with Isobutyraldehyde and Nitriles
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[5] Synthesis of 1-substituted 2-azaspiro[4.5]deca-6,9-dien-8-ones and 2-azaspiro[4.5]deca-1,6,9-trien-8-ones by condensation of 2,6-dimethylphenol with isobutyraldehyde and nitriles
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[9] A Three-Component Condensation of 2,5-Dialkyl-Phenols, Isobutyric Aldehyde, and Nitriles. Synthesis of New 2-Azaspiro[4.5]Deca-6,9-Dien-8-Ones and 2-Azaspiro[4.5]Deca-1,6,9-Trien-8-Ones
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