Acetylene Sesquiterpenoid Esters from the Green Alga Caulerpa prolifera Vangelis Smyrniotopoulos, Dennis Abatis, Leto-A. Tziveleka, Christina Tsitsimpikou, Vassilios Roussis, Anargyros Loukis, and Constantinos Vagias* School of Pharmacy, Department of Pharmacognosy and Chemistry of Natural Products, University of Athens, Panepistimioupolis Zografou, 157 71 Athens, Greece Received May 31, 2002 Sixteen secondary metabolites of the green alga Caulerpa prolifera have been isolated, and their chemical structures elucidated by analysis of their spectroscopic data. Two groups of metabolites have been established, with either a 1,2-dihydro- (2a-2i) or a 1,2,3,3′-tetrahydro-2,3-didehydro (3a-3f) caulerpenyne carbon backbone. The terminal vinyl acetoxy group of caulerpenyne was substituted by various fatty acid residues. The antifouling activity of the algal extract was tested in laboratory assays against two of the major groups of fouling organisms (bacteria, microalgae). Green algae of the family Caulerpaceae, represented by the single genus Caulerpa, are found worldwide, generally in shallow water tropical and subtropical marine habitats. Mediterranean species of Caulerpales are also known. The genus Caulerpa has been widely studied, and the struc- tures of many new compounds, such as triterpenoids and squalene derivatives, the nitrogen-containing compounds caulerpin and caulerpicin, and the diterpenoid alcohol caulerpol, have been described. 1-4 More recently, linear terpenoids possessing (or derived from) terminal E,E-1,4- diacetoxybutadiene moieties, like caulerpenyne, have been isolated from several Caulerpa species. 5-9 Unlike the former compounds, these latter metabolites, analogues of which are also isolated from phylogenetically related algae of the family Udoteaceae, appear to possess ichthyotoxic, cytotoxic, and feeding deterrent properties, thus aiding these algal species in enduring the great pressure in the tropics for food, space, and control of epibiont over- growth. 5,6,10-13 Marine fouling and corrosion caused by the growth of organisms on immersed surfaces generate serious and expensive problems in several maritime economic domains. Fouling development prevented by means of paints con- taining toxic compounds is associated with environmental and human health problems. Marine secondary metabolites might comprise a potential alternative for the prevention of fouling. As Caulerpa species are usually found in abundance and highly exposed in areas of significant herbivore populations, it seems likely that these uncalcified algae possess chemical deterrents to reduce predation. 1 In the course of our investigations toward the isolation of bioactive metabolites from marine sources, 14-16 we describe here the isolation and structural elucidation of 16 metabolites of the E,E-1,4-diacetoxybutadiene class and the antifouling efficacy of C. prolifera extract. Metabolites 2c, 2d, 2f-2i, and 3a-3f are reported for the first time. Results and Discussion The terpene esters isolated are grouped according to their structural similarity with respect to caulerpenyne (1). Caulerpenyne (1), which has been previously isolated from several Caulerpa species from the Mediterranean Sea (C. prolifera, C. taxifolia), 6,8,17 the Pacific Ocean, and the Caribbean Sea (C. prolifera, C. racemosa, C. taxifolia, C. lanuginosa, etc.), 4,5 was identified on the basis of its NMR and MS spectral data that were identical with those originally reported. 6,8 * To whom correspondence should be addressed. Tel: +32 10 7274590. Fax: +32 10 7274592. E-mail: vagias@pharm.uoa.gr. 21 J. Nat. Prod. 2003, 66, 21-24 10.1021/np0202529 CCC: $25.00 © 2003 American Chemical Society and American Society of Pharmacognosy Published on Web 11/27/2002