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

Research output: Contribution to journalArticlepeer-review

5 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 languageEnglish
Pages (from-to)287-293
Number of pages7
JournalJournal of Antibiotics
Volume69
Issue number4
DOIs
Publication statusPublished - 2016 Apr 1

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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