Hydroxylated Sclerosporin Derivatives from the Marine-Derived Fungus Cadophora malorum

Abstract

The marine-derived fungus Cadophora malorum was isolated from the green alga Enteromorpha sp. Growth on a biomalt medium supplemented with sea salt yielded an extract from which we have isolated sclerosporin and four new hydroxylated sclerosporin derivatives, namely 15-hydroxysclerosporin (2), 12-hydroxysclerosporin (3), 11-hydroxysclerosporin (4) and 8-hydroxysclerosporin (5). The compounds were evaluated in various biological activity assays. Compound 5 showed a weak fat-accumulation inhibitory activity against 3T3-L1 murine adipocytes.In recent years, research on the chemistry of marine organisms has experienced a tremendous increase, due to the need for compounds possessing bioactivity with possible pharmaceutical application or other economically useful properties. 1 From these organisms, marine fungi are recognized as a valuable source for new and bioactive secondary metabolites that have the potential to lead to innovations in drug therapy. 2 Sclerosporin is a rather rare antifungal and sporogenic cadinane-type sesquiterpene. 3,4 This substance, initially isolated from Sclerotinia fruticula showed an induction of asexual arthrospore formation in fungal mycelia.3 ,5 Interestingly, its (−)-form isolated from Diplocarpon mali did not showed sporogenic activity towards S. frutícula. 5,6 During our search for new natural products produced from the marinederived fungus Cadophora malorum, (+)-sclerosporin (1) and four new hydroxylated sclerosporin derivatives (2 -5) were isolated from a spore culture on agar-BMS media supplemented with artificial sea salt.The molecular formulae of compounds 2 -5 were deduced by HREIMS to be identical, i.e. C 15 H 22 O 3 , indicating five degrees of unsaturation. The 13 C NMR spectra for all four compounds showed 15 closely similar resonance signals, evidencing that each of the compound belonged to the same structural type. In each case a 13 C NMR downfield shifted resonance signal at δ 168 -170 was found, typical for a carboxylic acid functionality (C-14), whereas a further resonance signal at around δ 70 indicated a hydroxy substituted methylene for compounds 2 and 3, a hydroxy substituted methine for compound 5, and for compound 4 a hydroxylated quaternary carbon (see Table 1-Table 2, respectively). IR spectroscopic measurements showed a broad absorption band at 3300 cm −1 for 2 -5, also confirming the presence of a hydroxy substituent in each case. † Dedicated to the late Dr. John W. Daly of NIDDK, NIH, Bethesda, Maryland and to the late Dr. Richard E. Moore of the University of Hawaii at Manoa for their pioneering work on bioactive natural products. *To whom correspondence should be addressed. Tel.: +49228733747. Fax: +49228733250. g.koenig@uni-bonn.de. Supporting Information Available: 1 H and 13 C NMR, HREIMS, IR, CD spectra and other relevant information are included for compounds 1 -5. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript J Nat Prod. Author manuscript; available in PMC 2011 March 26....

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