Antibacterial clerodane diterpenes from Goldenrod (Solidago virgaurea) Courtney M. Starks * , Russell B. Williams, Matt G. Goering, Mark O’Neil-Johnson, Vanessa L. Norman, Jin-Feng Hu, Eliane Garo, Grayson W. Hough, Stephanie M. Rice, Gary R. Eldridge Lead Discovery and Rapid Structure Elucidation Group, Sequoia Sciences Inc., 1912 Innerbelt Business Center Drive, St. Louis, MO 63114, United States article info Article history: Received 23 December 2008 Received in revised form 7 August 2009 Available online 24 October 2009 Keywords: Goldenrod (or woundwort) Solidago virgaurea Asteraceae Clerodane Diterpene Solidagoic acid Antibacterial Staphylococcus aureus abstract Nine clerodane diterpenes, solidagoic acids C-I (1–7), cleroda-3,13(14)-dien-16,15:18,19-diolide (8) and cleroda-3,13(14)-dien-15,16:18,19-diolide (9) were isolated and characterised from the ethanol–ethyl acetate (1:1) extract of Solidago virgaurea. The structures were determined by NMR spectroscopic analy- sis. Several displayed moderate antibacterial activity against Staphylococcus aureus. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Antibacterial resistance among pathogenic bacteria is increas- ing, creating a need for new antibiotics in the drug development pipeline (Levy and Marshall, 2004; Taubes, 2008). Natural prod- ucts will likely be a major source of the chemical diversity needed to thwart multiple resistance mechanisms (Payne et al., 2007). In the course of our search for new antibacterial compounds from a taxonomically diverse plant collection, we applied a high- throughput natural product discovery approach (Eldridge et al., 2002) to Goldenrod (or woundwort) Solidago virgaurea L. (Astera- ceae). This plant is one of approximately 80 species of Solidago from North America, and has become naturalised in Europe (Mab- berley, 1997). It is now cultivated for local medicinal use in East- ern Europe (Sztefanov et al., 2002). Solidago species were an early focus of studies on the Asteraceae diterpenes, and many clerod- anes have been isolated from the genus (Seaman, 1990). Clerod- anes oxygenated at the six-position have been isolated previously from S. virgaurea (Goswami et al., 1984). Here we de- scribe two known (1, 9) and seven new (2–8) clerodanes from S. virgaurea. 2. Results and discussion An organic extract of S. virgaurea was subjected to normal phase flash chromatography and reversed phase HPLC to yield two known (1, 9) and seven new (2–8) cis-clerodane diterpenes (Fig. 1). Compounds 1, 2, 5, 7, 8, and 9 were isolated in microscale quantities using our high-throughput natural products isolation methods (Eldridge et al., 2002). Scaling up the purification led to the isolation of compounds 3, 4, and 6, as well as additional quan- tities of 1, 2, 7, 8, and 9 (5 was not found in the scaled-up isolation). Structures were determined using data acquired from 6500 lg of sample in a capillary microcoil NMR probe. Several of these com- pounds displayed moderate antibacterial activity against S. aureus (Table 1). The 1 H NMR spectrum of 1 displayed one doublet (d 0.79) and two singlet (d 0.96, 1.54) methyl signals, downfield signals at d 7.13 and 5.50, and a number of multiplets between d 1.3 and 2.5 (Table 2). This pattern was indicative of a clerodane-type diterpene with one modified methyl group. The 1D and 2D NMR spectra were consistent with the structure shown for 1,a cis-clerodane with an a, b-unsaturated c-lactone side chain. This compound had been re- ported previously as a synthetic derivative of solidagoic acid A (Anthonsen et al., 1973), which bears a b-furanoethyl side chain. The optical rotation of 1 (½a 25 D 50) closely matches that reported for solidagoic acid A in the same solvent ([a] D 58). Here, we assign 1 the name solidagoic acid C and present more complete NMR spec- troscopic data than was available in the original publication. 0031-9422/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2009.09.032 * Corresponding author. Tel.: +1 314 373 5181x107; fax: +1 314 373 5186. E-mail address: cstarks@sequoiasciences.com (C.M. Starks). Phytochemistry 71 (2010) 104–109 Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem