An efficient synthesis of cyercene A John E. Moses, Jack E. Baldwin * and Robert M. Adlington Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK Received 26 May 2004; revised 24 June 2004; accepted 29 June 2004 Available online 20 July 2004 Abstract—An efficient approach to the total synthesis of the marine derived polypropionate cyercene A is described. A key feature of the synthesis is the development of methodology for the diastereoselective Wadsworth–Emmons type condensation of a function- alised c-pyrone unit. Ó 2004 Elsevier Ltd. All rights reserved. 1. Introduction Pyrone-containing compounds are characteristically produced by a restricted group of marine molluscs of the order Sacoglossa. 1 These compounds, which are for- mally derived from a polyketide pathway, are associated with specific ecophysiological functions of the molluscs, since they may act as mediators in tissue regeneration and chemical defence. 2 Cyerce cristallina is an ascoglossan species whose body volume is mainly due to the presence of dorsal append- ages aposematically coloured in white and red. When attacked by predators this mollusc secretes a presumably toxic mucus and, if molested further, it detaches its cer- ata, which then exhibit prolonged contractions and carry on secreting large amounts of mucus. After the occurrence of the autonomic process, the mollusc pro- vides a striking example of regeneration by completely reproducing the cerata within only 7–10 days. Intrigued by the unusual display of tissue regeneration for such a complex organism, Marzo and co-workers undertook a program of research, aimed at characteris- ing some of the chemical signals involved in the chemical defence and regenerative processes of C. cristallina. Analysis of the molluscs cerata resulted in the isolation and characterisation of seven novel pyrone containing compounds, named the cyercenes (Fig. 1). 3 Of the seven compounds isolated, cyercene A 1 was found to be central to the signalling process responsible for controlling the amazing regenerative properties of the mollusc. 3,4 The unusual biological activity attributed to 1, along with its interesting structural features make cyercene A 1 a worthy synthetic target. As part of our continuing efforts directed towards understanding the origins of complex c-pyrone-contain- ing natural products, 5 we became interested in develop- ing a synthetic route to cyercene A 1, which could serve as a model for more complex systems. 0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2004.06.125 Keywords: Pyrone; Propionate; Wadworth–Emmons. * Corresponding author. Tel.: +44-0-1865-275-671; fax: +44-0- 1865275632; e-mail: jack.baldwin@chem.ox.ac.uk R 2 O O O R 1 = Cyercene A R 1 = Me, R 2 = Me 2 = Cyercene B R 1 = H, R 2 = H 3 = Cyercene 1 R = Me 4 = Cyercene 2 R = Et 5 = Cyercene 3 R = i Pr R 6 = Cyercene 4 R = Me 7 = Cyercene 5 R = Et O O R 1 O O O O Figure 1. Tetrahedron Letters 45 (2004) 6447–6448 Tetrahedron Letters