The oxidation profile at C-18 of furanocembranolides may provide a taxonomical marker for several genera of octocorals Enrique Dorta, a Ana R. D  ıaz-Marrero, a Inmaculada Brito, a Mercedes Cueto, a Luis D’Croz b,c and Jos e Darias a, * a Instituto de Productos Naturales y Agrobiologia, C.S.I.C., Avenida Astrof  ısico F. S  anchez, 3. Apartado 195, 38206 La Laguna, Tenerife, Canary Island, Spain b Smithsonian Tropical Research Institute, STRI, PO Box 2072, Balboa, Panama c Departamento de Biolog ıa Marina y Limnolog ıa. Estafeta Universitaria, Universidad de Panama, Panama Received 4 June 2007; revised 22 June 2007; accepted 27 June 2007 Available online 4 July 2007 Abstract—The furanocembranolides 1–3 along with the known compounds pukalide, pukalidealdehyde, epoxypukalide, and leptolide were isolated from Leptogorgia spp. and their structures were determined by spectroscopic evidences. An NMR-based method using Pirkle’s reagent at low temperature allowed us to determine the absolute configuration at C-10 of a g-butenolide unit embedded in a flexible furano- cembranolide network. The C-18 of furanocembranolides undergoes an oxidation cascade leading from a methyl group to a carboxylic acid/ ester that appears to be genus specific. We introduce the concept genus-specific oxidation, a feature that provides a chemotaxonomical marker for several genera of octocorals. This concept also allowed us to propose a biogenetic pathway for these compounds. Ó 2007 Elsevier Ltd. All rights reserved. 1. Introduction Octocorals of the genera Pseudopterogorgia, Alcyonium, Gersemia, Lophogorgia, Leptogorgia, and Sinularia have the ability to biosynthesize furanocembranolides, 1 highly oxygenated diterpenoids based on the 14-membered carbo- cyclic cembrane skeleton into which a substituted furan ring and a g-lactone subunit have become embedded. Stud- ies to date indicate that certain members of the family exhibit potent neurotoxicity, 2 in addition to antiinflammatory, 3 anti- feedant activity, 4 and other biological properties. 5 Furano- cembranolides have also been popular targets for total synthesis. 6 Based on a survey on marine furanocembranolides, 7 they may be divided into four classes: those in which the substit- uent at the C4 position is a CH 3 (class A), and those with a more highly oxidized substituent, CHO (class B), COOH (class C), and CO 2 Me (class D). The methyl group on the furan ring is prone to be oxidized in metabolites from Pseudopterogorgia, Lophogorgia, Leptogorgia, and Sinu- laria, the degree of oxidation varying from one genus to another. Thus, the genus Pseudopterogorgia is rich in furanocembranolides of classes A and C, but lacks furano- cembranolides of classes B and D. The genus Leptogorgia produces furanic aldehyde (class B) and methyl ester derivatives (class D) whereas the genus Lophogorgia and Sinularia exclusively biosynthesize aldehyde (class B) and methyl ester derivatives (class D), respectively. O R Class A: R= Me Class B: R= CHO Class C: R= COOH Class D: R= COOMe O O Cembrane skeleton 4 1 From the genera Alcyonium and Gersemia only furano- cembranolides of class A have been found, no oxidized cembranoids of classes B–D have been reported. 7 It is worth to note that no naturally occurring hydroxylic intermediate has ever been reported. 2. Results and discussion The search for marine natural products in benthic species from both sides of the Isthmus of Panama 8 prompted us to study the eastern Pacific octocoral Leptogorgia spp. In this paper, we report on the structures of three new furanocem- branolides 1–3 along with the known compounds pukalide 9 4, pukalidealdehyde 10 5, epoxypukalide 11 6, and leptolide 12 7 isolated from this species. Compounds 1–3, 4, and 6 fall in * Corresponding author. Tel.: +34 922252144; fax: +34 922260135; e-mail: jdarias@ipna.csic.es 0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2007.06.080 Tetrahedron 63 (2007) 9057–9062