Total Synthesis of Tiacumicin B Aglycone

  • Author: Veronika Belusa
  • Published Date: 25 December 2014
  • Source / Publisher: Angewandte Chemie International Edition/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
thumbnail image: Total Synthesis of Tiacumicin B Aglycone

Tiacumicin B (lipiarmycin A3, fidaxomicin) is an atypical macrolide antibiotic. It inhibits bacterial RNA polymerase and is used for the treatment of infections with Clostridium difficile, the most frequent cause of nosocomial diarrhea infections in the developed world. Tiacumicin B is also a potent inhibitor of Mycobacterium tuberculosis, but due to its limited oral bioavailability is unsuitable for systemic therapy.
Despite their biological profiles and intriguing structures, no total synthesis of any member of the tiacumicin/lipiarmycin/clostomicin family or the corresponding aglycones has been reported to date.

Florian Glaus and Karl-Heinz Altmann, ETH Zurich, Switzerland, have developed an efficient synthesis of the tiacumicin B aglycone.

The synthesis contains a high-yielding intramolecular Suzuki cross-coupling reaction for macrocyclic ring closure. Key steps in the synthesis of the macrocyclization precursor were a highly selective, one-pot Corey–Peterson olefination, which is based on a new thiophenol-mediated Z → E isomerization of an α, β-unsaturated corss-etathesis reaction, and an ene–diene cross-metathesis reaction.
Depending on the reaction conditions, the final deprotection leads to either the fully deprotected tiacumicin B aglycone or partially protected versions thereof.

Article Views: 3738

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

If you would like to reuse any content, in print or online, from, please contact us first for permission and consult our permission guidance prior to making your request

Follow on Facebook Follow on Twitter Follow on YouTube Follow on LinkedIn Follow on Instagram RSS Sign up for newsletters

Magazine of Chemistry Europe (16 European Chemical Societies) published by Wiley-VCH