A pyran-2-one and four meroterpenoids from Thapsia transtagana and their implication in the biosynthesis of transtaganolides Juan J. Rubal a , F.J. Moreno-Dorado a , Francisco M. Guerra a , Zacarı ´as D. Jorge a , Abderrahmane Saouf b , Mohamed Akssira b , Fouad Mellouki b , Rau ´ l Romero-Garrido a , Guillermo M. Massanet a, * a Departamento de Quı ´mica Orga ´ nica, Facultad de Ciencias, Universidad de Ca ´ diz, Puerto Real, 11510-Ca ´ diz, Spain b Faculte ´ des Sciences et Techniques, Universite ´ Hassan II Mohammedia, LCBA, UFR C35/97, BP 146 Mohammedia 20650, Morocco Received 28 May 2007; received in revised form 15 June 2007 Available online 31 July 2007 Abstract Four meroterpenoids (3a, 3b, 4 and 5), a prenylated pyran-2-one (2) along with the known compounds 7-O-geranylscopoletin (1), and thapsitranstagin (6) have been isolated from the roots of Thapsia transtagana. The presence of 1 and 2 supports the biogenetic hypothesis that transtaganolides, a group of bioactive metabolites, are meroterpenoids which come from an O-prenylated coumarin via successive pericyclic reactions. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Thapsia transtagana; Apiaceae; Meroterpenoids; Transtaganolides; Prenylated coumarin; Guaianolide; Secocoumarin; Thapsianolide; Biogenetic hypothesis 1. Introduction The genus Thapsia is constituted by ten species distrib- uted in the western Mediterranean area and extended to the Atlantic coast of the Iberian Peninsula and Morocco (Pujadas and Rosello ´, 2003). Despite its reduced extension, a relatively large number of secondary metabolites have been isolated from the genus Thapsia, sesquiterpenoids (Christensen et al., 1997) and phenylpropanoids (Liu et al., 2006), being the more signif- icants. Since the discovery of thapsigargins from Thapsia garganica (Rassmussen et al., 1978) the interest for the phy- tochemical studies on Thapsia has been increased. Thapsi- gargin, the lead compound which names the family and other members of this group of guaianolides are selective and irreversible inhibitors of the ubiquitous sarco-endo- plasmatic reticulum Ca 2+ ATPases (Treiman et al., 1998). Thapsigargin has also been shown to restore apoptotic function in cancer cell lines (Furuya et al., 1994). In the course of our evaluation of Thapsia species as a source of new thapsigargin analogues, we described a new group of secondary metabolites that we named tran- staganolides (Saouf et al., 2005). The origin of the very uncommon structure of transtaganolides is quite intrigu- ing. As their structures suggest a terpenoid nature, a bioge- netic route starting from geranyl pyrophosphate has been proposed by Appendino et al. (2005), although the same authors also proposed a quite different and more impres- sive way involving a phenol cleavage and a cascade pericy- clic process. 1 0031-9422/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2007.06.023 * Corresponding author. Tel.: +34 956 016366; fax: +34 956 16288. E-mail address: g.martinez@uca.es (G.M. Massanet). 1 In reference Appendino et al. (2005), the authors reported two new transtaganolides and named them as basiliolides. We consider that the generic name transtaganolides, previously suggested by us after the very first description of these compounds (Saouf et al., 2005) should prevail for all the members of the family for the sake of clarity. www.elsevier.com/locate/phytochem Phytochemistry 68 (2007) 2480–2486 PHYTOCHEMISTRY