An Expeditious Route to Fluorinated Rapamycin Analogues by Utilising Mutasynthesis

Rebecca J. M. Goss, Simon Lanceron, Abhijeet Deb Roy, Simon Sprague, Mohammed Nur-E-Alam, David L. Hughes, Barrie Wilkinson, Steven J. Moss

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Rapamycin is a drug with several important clinical uses. Its complex structure means that total synthesis of this natural product and its analogues is demanding and lengthy. A more expeditious approach is to utilise biosynthesis to enable the generation of otherwise synthetically intractable analogues. In order to achieve this, rules governing biosynthetic precursor substrate preference must be established. Through determining these rules and synthesising and administering suitable substrate precursors, we demonstrate the first generation of fluorinated rapamycin analogues. Here we report the generation of six new fluororapamycins.
Original languageEnglish
Pages (from-to)698-702
Number of pages5
JournalChemBioChem
Volume11
Issue number5
DOIs
Publication statusPublished - 2010

Keywords

  • PRECURSOR-DIRECTED BIOSYNTHESIS
  • immunosuppressants
  • fluorine
  • DERIVATIVES
  • ANTIBIOTICS
  • products
  • natural
  • biosynthesis
  • antitumor agents

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