Antibacterial Spirobisnaphthalenes from the North American Cup Fungus Urnula craterium Xue-Ting Liu, † William R. Schwan, ‡ Thomas J. Volk, § Marc Rott, ‡ Miaomiao Liu, † Pei Huang, † Zhong Liu, ⊥ Ying Wang, ∥ Nicholas C. Zitomer, § Cassandra Sleger, ‡ Scott Hartsel, Δ Aaron Monte,* ,O and Lixin Zhang* ,† † Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, People's Republic of China ‡ Department of Microbiology, University of Wisconsin−La Crosse, La Crosse, Wisconsin 54601, United States § Department of Biology, University of Wisconsin−La Crosse, La Crosse, Wisconsin 54601, United States ⊥ Guangzhoujinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, People's Republic of China ∥ Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, People's Republic of China Δ Department of Chemistry, University of Wisconsin−Eau Claire, Eau Claire, Wisconsin 54702, United States O Department of Chemistry and Biochemistry, University of Wisconsin−La Crosse, La Crosse, Wisconsin 54601, United States * S Supporting Information ABSTRACT: Urnucratins A−C(1−3), which possess an unusual bisnaphthospiroether skeleton with one oxygen bridge and one C−C bridge and represent a new subclass of bisnaphthalenes, were isolated from the North American cup fungus Urnula craterium. Their structures, including absolute configurations, were determined by means of HRMS, NMR, and quantum chemical CD calculations. Urnucratin A (1) was found to be active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Streptococcus pyogenes with MIC values of 2, 1, and 0.5 μg/mL, respectively. A ntibiotic-resistant bacteria continue to cause many harmful infections around the world. New anti-infective drugs are needed to treat these infections, and searching for compounds from diverse natural resources has been a key starting point in the development of new antimicrobials. 1 As part of our recent screening efforts, about 350 species of wild North American mushrooms and other macrofungi were examined for antibacterial activity, and two series of compounds with modest potencies were previously described. 2,3 In additional work, the crude extract obtained from the saprobic fungus Urnula craterium (“devil’s urn”) showed promising antibacterial activity. U. craterium is a species of cup fungus in the family Sarcosomataceae (Ascomycota) that parasitizes oak and other hardwoods. The distribution of U. craterium includes eastern North America, Europe, and Asia. Few studies have examined the bioactive metabolites produced by U. craterium, although a previous investigation identified several simple lactone-type compounds and one naphthalone. 4 In the present study, bioassay-guided isolation of secondary metabolites from U. craterium led to the purification and structure elucidation of three novel spirobisnaphthalenes, urnucratins A−C(1−3) (Figure 1), with broad activity against Gram-positive bacteria. These compounds contained an unusual bisnaphthospiroether skeleton and could be classified as a new chemical subclass of the spirodioxynaphthalenes that contain two 1,8-dihydroxynaphthalene (DHN)-derived spi- roether units bridged through a spiroether linkage. A related series of compounds containing a dimeric naphthalene structure, such as daldinol and its analogues, has been described previously. 5 Additionally, since the metabolite MK3018 was first isolated in 1989 from the fungus Tetroploa aristata, 6 more Received: March 22, 2012 Published: August 30, 2012 Figure 1. Structures of compounds 1−3. Article pubs.acs.org/jnp © 2012 American Chemical Society and American Society of Pharmacognosy 1534 dx.doi.org/10.1021/np300221a | J. Nat. Prod. 2012, 75, 1534−1538