Synthesis and structure-activity relationship study of FD-891: Importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells

Tomohiro Itagaki; Ayano Kawamata; Miho Takeuchi; Keisuke Hamada; Yoshiharu Iwabuchi; Tadashi Eguchi; Fumitaka Kudo; Takeo Usui; Naoki Kanoh

doi:10.1038/ja.2015.148

Synthesis and structure-activity relationship study of FD-891: Importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells

Tomohiro Itagaki, Ayano Kawamata, Miho Takeuchi, Keisuke Hamada, Yoshiharu Iwabuchi, Tadashi Eguchi, Fumitaka Kudo, Takeo Usui, Naoki Kanoh

PHA - Molecular Pharmaceutical Science

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

8 Citations (Scopus)

Abstract

Unified synthesis of FD-891 analogs and their structure-activity relationship are described. By using stereoselective allylation/crotylation and Evans aldol chemistry, six side-chain fragments having different length and terminus were synthesized. These fragments were coupled with a macrolactone fragment, improved synthesis of which was also developed here, to generate FD-891 and five truncated analogs. These synthetic compounds as well as three analogs obtained from fermentation of gene-disrupted Streptomyces graminofaciens mutants were tested for in vitro cytotoxic activity against HeLa cells. As a result, coexistence of the C8-C9 epoxide and side-chain terminus was found to be critical for the cytotoxic activity.

Original language	English
Pages (from-to)	287-293
Number of pages	7
Journal	Journal of Antibiotics
Volume	69
Issue number	4
DOIs	https://doi.org/10.1038/ja.2015.148
Publication status	Published - 2016 Apr 1

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10.1038/ja.2015.148

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title = "Synthesis and structure-activity relationship study of FD-891: Importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells",

abstract = "Unified synthesis of FD-891 analogs and their structure-activity relationship are described. By using stereoselective allylation/crotylation and Evans aldol chemistry, six side-chain fragments having different length and terminus were synthesized. These fragments were coupled with a macrolactone fragment, improved synthesis of which was also developed here, to generate FD-891 and five truncated analogs. These synthetic compounds as well as three analogs obtained from fermentation of gene-disrupted Streptomyces graminofaciens mutants were tested for in vitro cytotoxic activity against HeLa cells. As a result, coexistence of the C8-C9 epoxide and side-chain terminus was found to be critical for the cytotoxic activity.",

author = "Tomohiro Itagaki and Ayano Kawamata and Miho Takeuchi and Keisuke Hamada and Yoshiharu Iwabuchi and Tadashi Eguchi and Fumitaka Kudo and Takeo Usui and Naoki Kanoh",

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T2 - Importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells

AU - Itagaki, Tomohiro

AU - Kawamata, Ayano

AU - Takeuchi, Miho

AU - Hamada, Keisuke

AU - Iwabuchi, Yoshiharu

AU - Eguchi, Tadashi

AU - Kudo, Fumitaka

AU - Usui, Takeo

AU - Kanoh, Naoki

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AB - Unified synthesis of FD-891 analogs and their structure-activity relationship are described. By using stereoselective allylation/crotylation and Evans aldol chemistry, six side-chain fragments having different length and terminus were synthesized. These fragments were coupled with a macrolactone fragment, improved synthesis of which was also developed here, to generate FD-891 and five truncated analogs. These synthetic compounds as well as three analogs obtained from fermentation of gene-disrupted Streptomyces graminofaciens mutants were tested for in vitro cytotoxic activity against HeLa cells. As a result, coexistence of the C8-C9 epoxide and side-chain terminus was found to be critical for the cytotoxic activity.

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Synthesis and structure-activity relationship study of FD-891: Importance of the side chain and C8-C9 epoxide for cytotoxic activity against cancer cells

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