(2S,3R)-2-Aminododecan-3-ol, a New Antifungal Agent from the Ascidian Clavelina oblonga Miriam H. Kossuga, † John B. MacMillan, ‡ Evan W. Rogers, ‡ Tadeusz F. Molinski,* ,‡ Gislene G. F. Nascimento, § Rosana M. Rocha, ⊥ and Roberto G. S. Berlinck* ,† Instituto de Quı ´mica de Sa ˜ o Carlos, Universidade de Sa ˜ o Paulo, CP 780, CEP 13560-970, Sa ˜ o Carlos, SP, Brazil, Department of Chemistry, University of California, Davis, California 95616, Faculdade de Cie ˆ ncias da Sau ´ de, Universidade Metodista de Piracicaba, Rodovia do Ac ¸ u ´ car, Km 156, 13400-901 Piracicaba, SP, Brazil, and Departamento de Zoologia, Setor de Cie ˆ ncias Biolo ´ gicas, Universidade Federal do Parana ´ , 81531-990, CP 19020, Curitiba, Parana ´ , Brazil Received July 2, 2004 A new antifungal agent, (2S,3R)-2-aminododecan-3-ol (1), has been isolated from the ascidian Clavelina oblonga collected in Brazil. The structure of 1 was established by analysis of spectroscopic data, including absolute stereochemistry determined by circular dichroism analysis of the dibenzoyl derivative 2. Compound 1 displayed antifungal activity against Candida albicans ATCC 10231 with a MIC of 0.7 μg/ mL and against Candida glabrata with a MIC of 30 μg/mL. Candida species are among the most common causes of fungal infections ranging from non-life-threatening muco- cutaneous illnesses to disseminated mycoses that affect blood and organs. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. Candidiasis affects mainly immunocompromised patients, the newborns, women, and elderly people. 1 The importance of antifungal chemotherapy continues to evolve rapidly because invasive fungal infections in immunocom- promised patients become increasingly significant. Re- cently, new antifungal agents, such as voriconazole and caspofungin, 2 have entered the clinical arena. In addition, new diagnosis methodologies for the evaluation of fungal infections, such as antifungal susceptibility testing (AFST), have been recently introduced, due to the intrinsic resis- tance of Candida krusei, decreased susceptibility of Can- dida glabrata, and development of resistance by Candida albicans (in mucosal disease in AIDS). 3,4 The availability of new classes of antifungal agents enhances opportunities for combination therapy against infections that are notori- ously difficult to treat. However, the importance in finding new effective antifungal agents cannot be dismissed. Continuing efforts in the laboratory and well-designed collaborative clinical trials are needed in order to provide opportunities of lasting benefit for patients at risk for or suffering from life-threatening invasive fungal infections. 1 Ongoing efforts toward the search for new natural antifungal agents from marine organisms have been re- cently reviewed, 5 indicating that marine invertebrates and microorganisms are good sources of new antifungal agents with distinct mechanisms of action. During our current search for new antifungal agents from marine sources, we observed that the crude extract of the ascidian Clavelina oblonga (Herdman, 1880) displayed antibiotic activity against Staphyloccocus aureus ATCC 25923, oxacillin- resistant S. aureus, and Candida albicans ATCC 10231. Bioassay-guided fractionation yielded the antifungal agent (2S,3R)-2-aminododecan-3-ol (1), which was strongly active against C. albicans (MIC of 0.7 ( 0.05 μg/mL) and moderately active against C. glabrata (MIC of 30.0 μg/mL). The activity of 1 against C. albicans is comparable to the antifungal activity of the clinically used antifungal agents nystatin (MIC between 1.0 and 4.0 μg/mL) and ketocona- zole (MIC between 0.01 and 1 μg/mL). Marine-derived 2-amino-alkanols and their unsaturated derivatives are commonly encountered in tunicates and some sponges. 6 The carbon chain length of these sphingolipid derivatives vary from C 12 to C 30 . 7,8 Polyunsaturated C 14 variants, such as xestoaminols from the sponge Xestospongia sp. 9 and obscuraminol A from the Mediterranean tunicate Pseudo- distoma obscurum, 10 are the most frequently reported. We describe herein the isolation and structure elucidation of the simplest member described to date, the C 12 saturated amino alcohol (2S,3R)-2-aminododecan-3-ol (1) from Claveli- na oblonga. (2S,3R)-2-Aminododecan-3-ol (1) was isolated as an optically active glassy solid, [R] 29 D +4.5° (c 0.22, MeOH). The HRCIMS analysis showed a quasi-molecular parent ion peak [M + H] + at m/z 202.21730 (calcd 202.21709) corresponding to the formula C 12 H 28 NO. Analysis of NMR data ( 1 H, BBD and DEPT 13 C, 1 H- 1 H COSY, HMQC, and * To whom correspondence should be addressed. Tel: +55-16-2739954. Fax: +55-16-2739952. E-mail: rgsberlinck@iqsc.usp.br. † Universidade de Sa ˜ o Paulo. ‡ University of California, Davis. § Universidade Metodista de Piracicaba. ⊥ Universidade Federal do Parana ´. 1879 J. Nat. Prod. 2004, 67, 1879-1881 10.1021/np049782q CCC: $27.50 © 2004 American Chemical Society and American Society of Pharmacognosy Published on Web 09/24/2004