Skipped unsaturation, in the form of 1,4-dienes, is common a feature of certain classes of natural products. It can be found in simple acyclic molecules such as fatty acids, but it also frequently occurs in more complex macrocyclic compounds. One such family of natural products is the phacelocarpus pyrones, nine macrocyclic pyronyl ethers isolated from the Australian red alga Phacelocarpus labillardieri between 1982 and 1995 (e.g. compounds 1 �5 ).1-4 These intriguing molecules contain a (Z,Z)-1,4-diene motif which is in turn skipped to an alkyne. In some cases this forms part of an extended skipped system with a pyronyl enol ether, a substructure found only in this family of compounds. This combination of functionality makes the synthesis of compounds such as these challenging, with the result that to date no total synthesis of any of the phacelocarpus pyrones is reported. We have sought a robust and general route to the synthesis of compounds of this type to obtain material for structure�activity studies. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/241nm/uploads/73938_figure.jpg' alt='' /> Figure 1 Selected phacelocarpus pyrones.A number of routes could be envisaged, but in order to develop a mild, robust and convergent route to the macrocyclic ring it was decided to use a model system in which the pyrone unit of 1 or 2 is replaced with a more stable benzene ring. We therefore present progress towards the synthesis of 6 , the retrosynthetic analysis of which is shown in Scheme 1, starting from the five fragments 9 �13 . Key discoveries include establishment of an efficient route to stannane 8 , and optimisation of the p-allyl Stille macrocyclisation. Scheme 1 Retrosynthetic analysis of compound 6 .References 1. Kazlauskas, R.; Murphy, P. T.; Wells, R. J.; Blackman, A. J., Aust. J. Chem.,1982 , 35, 113�120.2. Shin, J.; Paul, V. J.; Fenical, W., Tetrahedron Lett.,1986 , 27, 5189�5192.3. Blackman, A. J.; Bremner, J. B.; Paano, A. M. C.; Skerratt, J. H.; Swann, M. L., Aust. J. Chem.,1990 , 43, 1133�1136.4. Murray, L.; Currie, G.; Capon, R. J., Aust. J. Chem.,1995 , 48, 1485�1489.

Developing methodologies for the synthesis of macrocyclic natural products containing skipped alkenes

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.