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A new chloro-trinoreremophilane sesquiterpene 1, three new chlorinated eremophilane sesquiterpenes 2–4, together with a known compound, eremofortine C (5), were isolated from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1. Structures were established using IR, HRMS, 1D and 2D NMR techniques. In addition, the plausible metabolic network of these isolated products is proposed. Compound 1 showed moderate cytotoxic activity against HL-60 and A549 cancer cell lines.

dione (7), were isolated from the marine-derived fungus Aspergillus flavus. Their structures were determined by analysis of spectroscopic data. The cytotoxicities of compounds 1 and 2 were studied using HL-60, Key words: Aspergillus flavus, cyclopiazonic acid, cytotoxic activity.α-Cyclopiazonic acid (α-CPA) was a mycotoxic metabolite first isolated from Penicillium cyclopium Westling [1]. Since then, several other Penicillium and Aspergillus strains, including P. camembert and A. flavus and A. tamarii, were also found to produce α-CPA [2-4]. It has a range of biological activities, most notably Ca 2+ -ATPase inhibition, and can be used as a tool for the elucidation of intracellular Ca 2+ influx [5][6][7]. In the course of our search for new anticancer compounds from marine microorganisms, iso-α-cyclopiazonic acid (iso-α-CPA) (1) and α-CPA (2), together with three mycotoxins: aflatoxin B 1 (AFB 1 ) (3), aflatoxin Q 1 (AFQ 1 ) (4), and O-methylsterigmatocystin (OMST) (5); two diketopiperazine alkaloids: ditryptophenaline (6) and 3-[(1H-indol-3-yl)methyl]-6-benzylpiperazine-2,5-dione (7), were isolated from the A. flavus strain (c-f-3) isolated from marine algae, collected in Putian Pinghai, China. Compound 1 was first synthesized by Holzapfel in 1968 and isolated as a natural product for the first time. In this paper, we report the isolation and structure elucidation of 1, and the cytotoxic activities and structure-activity relationships of 1 and 2.Compound 1 shows a quasi-molecular ion peak at m/z 337 [M+H] + in the positive ESI-MS, and together with the 1 H and 13 C NMR spectra, supported the molecular formula of 1 (C 20 H 20 N 2 O 3 ) as 2. 1 H and 13 C NMR data (Table 1) disclosed the existence of eight sp 2 quaternary carbons, four sp 2 methines, three sp 3 methines, one sp 3 quaternary carbon, one sp 3 methylene, and three methyl groups. The 13 C NMR spectrum of 1 showed the characteristic carbon signals assignable to amide (δ C 173.2), ketone (δ C 195.0), and enol (δ C 183.1, 107.1), indicating that 1 possessed a tetramic acid ring. Four lower-field proton signals at δ H 6.89 (s), 7.11 (d, J = 8.0 Hz), 7.02 (dd, J = 8.0, 7.1 Hz), and 6.78 (d, J = 7.1 Hz), together with eight olefinic carbons (δ C 123.5 d, 109.1 s, 129.9 s, 116.3 d, 120.8 d, 108.7 d, 134.6 s, 128.4 s), suggested the presence of a disubstituted indole ring. Comparison of the NMR spectral data (Table 1) of 1 with those of 2 showed that 1 has the same planar structure as 2. The 1 H NMR data of 1 differed from those of 2 only in the chemical shifts of H-4 (δ H 3.78), H-5 (δ H 4.64), and H-11 (δ H 3.27), which shifted 0.10, 0.53, and 0.67 ppm more downfield than 2, respectively; and H-21 (δ H 0.85) and H-22 (δ H 1.48), which shifted 0.75 and 0.2 ppm more upfield than 2; further comparison of their CD data suggested that the only difference was the stereochemistry of C-5, viz 2 has S configuration, while 1 has R. So 1 was identified as iso-α-cyclopiazonic acid, in agreement with the reported NMR and CD data in the literature [1,8].

Chemical investigation of an Antarctic deepsea derived fungus Penicillium sp. PR19 N-1 yielded five new eremophilane-type sesquiterpenes 1–5 and a new rare lactam-type eremophilane 6, together with three known compounds 7–9. The structures of these diverse sesquiterpenes were determined by extensive NMR and mass spectroscopic analyses. Compounds 1, 2, 4–6, 8 and 9 were evaluated for their cytotoxities against HL-60 and A-549 human cancer cell lines, and 5 was the most active one with IC50 value of 5.2 lM against the A-549 cells.