Some limitations of an approach to the assembly of bryostatins by ring-closing metathesis

Research output: Contribution to journalArticle

  • Authors:
  • Raphaël Dumeunier
  • Thomas Gregson
  • Somhairle MacCormick
  • Hiroki Omori
  • Eric J. Thomas

Abstract

Preliminary studies into the use of ring-closing metathesis (RCM) in a convergent approach for the total synthesis of bryostatins are described. An ester that would have provided an advanced intermediate for a synthesis of a 20-deoxybryostatin by a RCM was prepared from an unsaturated acid and alcohol corresponding to the C1-C16 and C17-C27 fragments. However, studies of the formation of the C16-C17 double-bond by RCM were not successful and complex mixtures of products were obtained. To provide an insight into factors that may be involved in hindering RCM in this system, a slightly simplified C1-C16 acid and modified C17-C25 alcohols were prepared and their use for the synthesis of analogues of bryostatins was investigated. Although only low yields were obtained, it appeared that macrolides analogous to the bryostatins can be prepared by RCM, using the Grubbs II catalyst, if the precursors lack the two methyl groups at C18. RCM was not observed, however, for substrates in which these methyl groups were present.

Bibliographical metadata

Original languageEnglish
Pages (from-to)2768-2783
Number of pages16
JournalOrganic and Biomolecular Chemistry
Volume15
Issue number13
Early online date24 Feb 2017
DOIs
StatePublished - 2017