Formal total synthesis of fostriecin by 1,4-asymmetric induction with an alkyne-cobalt complex

Yujiro Hayashi, Hirofumi Yamaguchi, Maya Toyoshima, Kotaro Okado, Takumi Toyo, Mitsuru Shoji

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The synthesis of a protected dephosphofostriecin, and thereby a formal synthesis of fostriecin, has been accomplished. The synthetic challenges were the construction of four stereogenic centers and the conformationally labile cis-cis-trans-triene moiety. Previous total syntheses have employed at least two asymmetric reactions that required the use of an external chiral auxiliary. Although remote stereoinduction in a 1,4-relationship is considered difficult, we have developed a notable 1,4-asymmetric induction that utilizes an alkyne-cobalt complex for the control of C5 stereochemistry by the C8 stereogenic center. The stereochemistry at C11 was established by 1,3-asymmetric induction with a higherorder alkynyl-zinc reagent. Thus, only one asymmetric reaction requiring an external chiral auxiliary was employed in this route. The labile cis-cis-transtriene unit was constructed at a late stage of the synthesis by diastereoselective coupling of a dienyne and an aldehyde unit, followed by reduction.

Original languageEnglish
Pages (from-to)10150-10159
Number of pages10
JournalChemistry - A European Journal
Volume16
Issue number33
DOIs
Publication statusPublished - 2010 Sep 3

Keywords

  • Alkynes
  • Asymmetric synthesis
  • Cobalt
  • Diastereoselectivity
  • Fostriecin

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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    Hayashi, Y., Yamaguchi, H., Toyoshima, M., Okado, K., Toyo, T., & Shoji, M. (2010). Formal total synthesis of fostriecin by 1,4-asymmetric induction with an alkyne-cobalt complex. Chemistry - A European Journal, 16(33), 10150-10159. https://doi.org/10.1002/chem.201000795