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Total synthesis of the tiacumicin B (lipiarmycin A3/fidaxomicin) aglycone.
Journal article

Total synthesis of the tiacumicin B (lipiarmycin A3/fidaxomicin) aglycone.

  • Glaus F Swiss Federal Institute of Technology (ETH) Zürich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, HCI H405, Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
  • Altmann KH
  • 2014-12-17
Published in:
  • Angewandte Chemie (International ed. in English). - 2015
Corey-Peterson olefination
Suzuki coupling
macrolides
tiacumicin
total synthesis
Aminoglycosides
Crystallography, X-Ray
Fidaxomicin
English Tiacumicin B (lipiarmycin A3, fidaxomicin) is an atypical macrolide antibiotic which is used for the treatment of Clostridium difficile infections. Tiacumicin B is also a potent inhibitor of Mycobacterium tuberculosis, but due to its limited oral bioavailability is unsuitable for systemic therapy. To provide a basis for structure-activity studies that might eventually lead to improved variants of tiacumicin B, we have developed an efficient approach to the synthesis of the tiacumicin B aglycone. The synthesis features a high-yielding intramolecular Suzuki cross-coupling reaction to effect macrocyclic ring closure. Key steps in the synthesis of the macrocyclization precursor were a highly selective, one-pot Corey-Peterson olefination and an ene-diene cross-metathesis reaction. Depending on the reaction conditions, the final deprotection delivered either the fully deprotected tiacumicin B aglycone or partially protected versions thereof.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/153491
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