Seminar: Dr Irene de Silvestro - BIOMIMETIC TOTAL SYNTHESIS OF THYMARNICOL

Thursday, 28 September 2017 - 12:00pm – Thursday, 28 September 2017 - 1:00pm  |  Chem Sci M11

Speaker: Dr Irene de Silvestro

The use of biomimetic approaches often results in the development of very short and efficient synthetic routes toward natural products. The inspiration taken from nature enabled the first biomimetic total synthesis of thymarnicol, a naturally occurring dimeric thymol-derivative isolated from Arnica sachalinensis.1,2 This was accomplished in 6 steps3 from commercially available starting materials. A detailed discussion of the successful synthesis and several failed approaches will be presented. Key to the success of the synthesis was a biomimetic hetero-DielsAlder dimerization, which provides compelling evidence in support of the biosynthetic dimerization pathway proposed by Passreiter and co-workers.1 The origins of the remarkable regioselectivity observed in the hetero-DielsAlder cycloaddition have been investigated. DFT calculations showed that this transformation proceeds through a rare example of C2-symmetric bis-pericyclic transition state. It has been discovered, however, that the subsequent oxidation occurs spontaneously when the substrate is exposed to air and visible light.

  1. Passreiter, C. M.; Willuhn, G.; Weber, H.; Schleifer, K-J. Tetrahedron, 1999, 55, 2997.
  2. Passreiter, C. M.; Weber, H.; Bläser, D.; Boese, R. Tetrahedron, 2002, 58, 279.
  3. De Silvestro, I.; Drew, S. L.; Nichol, G. S.; Duarte, F.; Lawrence A. L. Angew. Chem. Int. Ed., 2017, 56, 6813.