10.1021/ol401490u r 2013 American Chemical Society Published on Web 06/26/2013 ORGANIC LETTERS 2013 Vol. 15, No. 14 3487–3489 Oleaceran: A Novel Spiro[isobenzofuran- 1,2 0 -naptho[1,8-bc]furan] Isolated from a Terrestrial Streptomyces sp. Ritesh Raju, † Oleksandr Gromyko, ‡ Viktor Fedorenko, ‡ Andriy Luzhetskyy, † and Rolf M € uller* ,† Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Pharmaceutical Biotechnology, Saarland University, Campus C2 3, 66123 Saarbr € ucken, Germany, and Department of Genetics and Biotechnology, Ivan Franko National University of L’viv, Grushevskogo st. 4, L’viv 79005, Ukraine rom@mx.uni-saarland.de Received May 27, 2013 ABSTRACT Chemical analysis of a terrestrial-derived Streptomyces sp. Lv20195 cultivated from the root zone of Olea europea yielded oleaceran, 1, possessing a novel spiro[isobenzofuran-1,2 0 -naptho[1,8-b,c]furan] carbon skeleton. The structure of 1 was determined by detailed spectroscopic analysis. Actinomycetes have been an important source of novel secondary metabolites for many decades now, making this order of bacteria an important source for the discovery of rare and novel chemical entities. 1 Novel secondary meta- bolites reported from actinomycetes, cultivated from plant rhizospheres, have already led to some promising structur- al novelty. Noteworthy examples include alchivemycin A, 2 indotertine A, 3 juniperolide A, 4 and leopolic acid A. 5 One such strain (Lv20-195) came to our attention, based on our initial in-house chemical profiling. Strain Lv20-195, later identified as a Streptomyces sp., was cultivated from the rhizosphere of the plant Olea europea showing an interesting chemical profile. The strain was cultivated in a 5 L Erlenmeyer flask containing 1.5 L of M1 media for 8 days at 150 rpm, after which the whole broth was extracted with an equal volume of EtOAc. The resulting crude extract (178 mg) was then sequentially triturated against hexane, dichloromethane, and methanol. The dichloromethane fraction was then later subjected to reversed-phase semipreparative HPLC (Zorbax, C 8 , 9.6 mm  250 mm, 5 μm; 10 100% MeCN/H 2 O; 3 mL/min) to yield oleaceran, 1 (2.5 mg), as an amorphous brownish solid. HRESI(þ)MS analysis of 1 ([R] D = þ36.0) returned a pseudomolecular ion (321.1124 [M þ H] þ ) consistent with a molecular formula (C 20 H 16 O 4 , Δmmu 0.4) requiring 13 double bond equivalents (DBE). The 13 C, edHSQC, and 1 H NMR established a total carbon count of 20 and 16 protons, represented by 1 methylene, 2 tertiary methyls, † Saarland University. ‡ Ivan Franko National University of L'viv. (1) B erdy, J. J. Antibiot. 2005, 58 (1), 1–26. (2) Igarashi, Y.; Kim, Y.; In, Y.; Ishida, T.; Kan, Y.; Fujita, T.; Iwashita, T.; Tabata, H.; Onaka, H.; Furumai, T. Org. Lett. 2010, 12, 3402–3405. (3) Che, Q.; Zhu, T.; Qi, X.; M andi, A.; Kurt an, T.; Mo, X.; Li, J.; Gu, Q.; Li, D. Org. Lett. 2012, 14, 3438–3441. (4) Raju, R.; Gromyko, O.; Fedorenko, V.; Luzhetskyy, A.; Plaza, A.; M€ uller, R. Org. Lett. 2012, 23, 5860–5863. (5) Raju, R.; Gromyko, O.; Fedorenko, V.; Luzketskyy, A.; M€ uller, R. Tetrahedron Lett. 2012, 53, 6300–6301.