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

Shinichiro Fuse, Kennichi Inaba, Motoki Takagi, Masahiro Tanaka, Takatsugu Hirokawa, Kohei Johmoto, Hidehiro Uekusa, Kazuo Shin-ya, Takashi Takahashi, Takayuki Doi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)180-184
Number of pages5
JournalEuropean Journal of Medicinal Chemistry
Volume66
DOIs
Publication statusPublished - 2013 Jan 1

Keywords

  • Anticancer agent
  • Spiroacetal
  • Spirocycle
  • Spiromamakone A
  • Spiropreussione B

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Design and synthesis of 2-phenyl-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-onesas potential anticancer agents starting from cytotoxic spiromamakone A'. Together they form a unique fingerprint.

  • Cite this