Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A

Thomas O Ronson; Michael J Burns; Martin H H Voelkel; Kieren J Evans; Jason M Lynam; Richard J K Taylor; Ian J S Fairlamb

doi:10.1002/chem.201504089

Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A

Chemistry. 2015 Dec 21;21(52):18905-9. doi: 10.1002/chem.201504089. Epub 2015 Nov 16.

Authors

Thomas O Ronson¹, Michael J Burns¹, Martin H H Voelkel¹, Kieren J Evans¹, Jason M Lynam¹, Richard J K Taylor², Ian J S Fairlamb³

Affiliations

¹ Department of Chemistry, University of York, York, YO10 5DD (UK).
² Department of Chemistry, University of York, York, YO10 5DD (UK). richard.taylor@york.ac.uk.
³ Department of Chemistry, University of York, York, YO10 5DD (UK). ian.fairlamb@york.ac.uk.

PMID: 26568186
DOI: 10.1002/chem.201504089

Abstract

The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including Au(I)-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products.

Keywords: dienes; macrocycles; natural products; palladium; total synthesis.

Publication types

Research Support, Non-U.S. Gov't