Lamellodysidines A and B, Sesquiterpenes Isolated from the Marine Sponge Lamellodysidea herbacea Masumi Torii, † Hikaru Kato, † Yuki Hitora, † Esther D. Angkouw, ‡ Remy E. P. Mangindaan, ‡ Nicole J. de Voogd, § and Sachiko Tsukamoto* ,† † Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan ‡ Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia § Naturalis Biodiversity Center, P.O. Box 9517, 2300 RA Leiden, The Netherlands * S Supporting Information ABSTRACT: Four new sesquiterpenes, lamellodysidines A and B, O,O- dimethyllingshuiolide A, and 11-epi-O,O-dimethyllingshuiolide A (1-4), were obtained from the marine sponge, Lamellodysidea herbacea, collected in Indonesia. Their planar structures were elucidated by analysis of spectroscopic data. The absolute configurations of the new compounds were determined by the calculated ECD spectra. Compound 1 has a unique carbon framework, and 2 is a new nitrogenous sesquiterpene. M arine sponges are known to be rich sources of biologically active and structurally unique compounds. 1,2 A large number of marine natural products have been discovered from the order of Dictyoceratida, 3 which is well- known as a rich source of structurally highly diverse terpenes including sesterterpenes, 4-7 norsesterterpenes, 8 sesquiterpene quinones, 9-11 and furan-containing terpenes. 12-14 The chem- ical diversity of terpenes reported from Dictyoceratida is fascinating from the viewpoints of pharmacological properties and biosynthetic studies, and continuous efforts to explore new chemical scaffolds from natural sources are in great demand. 15 In our ongoing research into novel metabolites from marine sponges, we found that an extract of the sponge, L. herbacea, collected in Indonesia showed cytotoxic and antimicrobial activities, and we isolated 2-(2′-bromophenoxy)-3,4,5,6-tetra- bromophenol 16 and 2-(2′,4′-dibromophenoxy)-4,6-dibromo- phenol 17 as the biologically active entities. Together with these metabolites, four new sesquiterpenes, lamellodysidines A and B, O,O-dimethyllingshuiolide A, and 11-epi-O,O-dimethyl- lingshuiolide A (1-4), and a known sesquiterpene, O-methyl nakafuran-8 lactone 18 (5), were isolated. Compound 1 is the first natural product found to possess an unprecedented bridged polycyclic skeleton, and 2 is a new nitrogen-containing sesquiterpene. ■ RESULTS AND DISCUSSION Lamellodysidine A (1) has the molecular formula of C 15 H 20 O 3 , which was determined by HRESIMS. The 1 H NMR spectrum showed a Z-olefin(δ H 5.80 (H-11) and 6.18 (H-10), 3 J HH = 8.2 Hz), a methine bearing two oxygen atoms (δ H 5.24 (d, J = 3.8 Hz, H-1)), and three methyls (δ H 0.78 (s, H-14), 0.81 (d, J = 7.3 Hz, H-15), and 1.14 (s, H-13)) (Table 1). The 13 C NMR and DEPT spectra indicated the presence of a carbonyl carbon (δ C 178.2, C-9), two protonated olefin carbons (δ C 132.5 (C- 10) and 135.8 (C-11)), two methylenes (δ C 33.4 (C-7) and 39.4 (C-6)), four methines (δ C 38.5 (C-3), 47.1 (C-4), 60.7 (C- 2), and 99.4 (C-1)), three methyls (δ C 15.8 (C-13), 17.2 (C- 15), and 18.6 (C-14)), and three additional quaternary carbons (δ C 49.0 (C-5), 51.6 (C-12), and 57.7 (C-8)) (Table 1). The planar structure of 1 was determined by detailed analysis of 2D NMR spectroscopic data. The COSY spectrum revealed the presence of two spin systems, H-1/H-2/H-3(/H-10/H-11)/H- 4/H-15 and H-6/H-7 (Figure 1a). The HMBC correlations from H-7 to C-2 and C-8, from H-13 to C-5, C-8, C-11, and C- 12, and from H-14 to C-4, C-5, C-6, and C-12 established a Received: July 16, 2017 Article pubs.acs.org/jnp © XXXX American Chemical Society and American Society of Pharmacognosy A DOI: 10.1021/acs.jnatprod.7b00610 J. Nat. Prod. XXXX, XXX, XXX-XXX