Synthesis and biological evaluation of a beauveriolide analogue library

Kenichiro Nagai; Takayuki Doi; Takafumi Sekiguchi; Ichiji Namatame; Toshiaki Sunazuka; Hiroshi Tomoda; Satoshi Omura; Takashi Takahashi

doi:10.1021/cc050084d

Synthesis and biological evaluation of a beauveriolide analogue library

Kenichiro Nagai, Takayuki Doi, Takafumi Sekiguchi, Ichiji Namatame, Toshiaki Sunazuka, Hiroshi Tomoda, Satoshi Omura, Takashi Takahashi

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

Abstract

Synthesis of beauveriolide III (1b), which is an inhibitor of lipid droplet accumulation in macrophages, was achieved by solid-phase assembly of linear depsipeptide using a 2-chlorotrityl linker followed by solution-phase cyclization. On the basis of this strategy, a combinatorial library of beauveriolide analogues was carried out by radio frequency-encoded combinatorial chemistry. After automated purification using preparative reversed-phase HPLC, the library was tested for inhibitory activity of CE synthesis in macrophages to determine structure-activity relationships of beauveriolides. Among them, we found that diphenyl derivative 7{9,1} is 10 times more potent than 1b.

Original language	English
Pages (from-to)	103-109
Number of pages	7
Journal	Journal of Combinatorial Chemistry
Volume	8
Issue number	1
DOIs	https://doi.org/10.1021/cc050084d
Publication status	Published - 2006 Jan 1
Externally published	Yes

ASJC Scopus subject areas

Drug Discovery
Organic Chemistry
Chemistry(all)
Discrete Mathematics and Combinatorics

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10.1021/cc050084d

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AU - Nagai, Kenichiro

AU - Doi, Takayuki

AU - Sekiguchi, Takafumi

AU - Namatame, Ichiji

AU - Sunazuka, Toshiaki

AU - Tomoda, Hiroshi

AU - Omura, Satoshi

AU - Takahashi, Takashi

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Synthesis and biological evaluation of a beauveriolide analogue library

Abstract

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