Enantio- and diastereoselective total synthesis of EI-1941-1, -2, and -3, inhibitors of interleukin-1β converting enzyme, and biological properties of their derivatives

Mitsuru Shoji, Takao Uno, Hideaki Kakeya, Rie Onose, Isamu Shiina, Hiroyuki Osada, Yujiro Hayashi

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The first asymmetric total synthesis of EI-1941-1, -2, and -3, inhibitors of the interleukin-1β converting enzyme (ICE), has been accomplished, starting from a chiral epoxy iodoquinone 11, a key intermediate in our total synthesis of epoxyquinols A and B. Despite a failure to synthesize the inhibitors by our postulated biosynthetic route, we were able to diastereoselectively synthesize them via an intramolecular carboxypalladation with the key steps being a 6-endo cyclization mode followed by β-hydride elimination. The investigation of the biological properties of EI-1941-1, -2, and -3 and their derivatives disclosed them to be potent and effective ICE inhibitors with less cytotoxicity than EI-1941-1 and -2 in a cultured cell system.

Original languageEnglish
Pages (from-to)9905-9915
Number of pages11
JournalJournal of Organic Chemistry
Volume70
Issue number24
DOIs
Publication statusPublished - 2005 Nov 25

ASJC Scopus subject areas

  • Organic Chemistry

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