Linear pyrrolosesterterpenes from a sponge Sarcotragus species

Linear pyrrolosesterterpenes from a sponge Sarcotragus species

Biochemical Systematics and Ecology 34 (2006) 774e776 www.elsevier.com/locate/biochemsyseco Linear pyrrolosesterterpenes from a sponge Sarcotragus sp...

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Biochemical Systematics and Ecology 34 (2006) 774e776 www.elsevier.com/locate/biochemsyseco

Linear pyrrolosesterterpenes from a sponge Sarcotragus species Yonghong Liu a,*, Jee H. Jung b, Si Zhang a a

Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510-301, China b College of Pharmacy, Pusan National University, Busan 609-735, Korea Received 7 April 2006; accepted 8 June 2006

Keywords: Marine sponge; Sarcotragus; Pyrrolosesterterpene

1. Subject and source The sponge was collected in July 1998 (15e25 m depth), off the coast of Jeju Island, Korea. The specimen was identified as Sarcotragus sp. by Prof. Chung Ja Sim, Hannam University. A voucher specimen of the sponge (registry No. Por. 33) was deposited in the Natural History Museum, Hannam University, Daejon, Korea, and has been described elsewhere (Liu et al., 2001). 2. Previous work Sponges of the genus Sarcotragus were reported to contain compounds such as variabilin (Perry et al., 1987), (7E,12E,20E)-variabilin, (7E,12Z,20Z)-variabilin, 8-hydroxy-(12E, 20Z)-variabilin, 14-furan-3-yl-3,7,11-trimethyltetradeca-7,11-dienoic acid (Barrow et al., 1988), sarcochromenol sulfates AeC and sarcohydroquinone sulfates AeC (Stonik et al., 1992), octa- and nonaprenylhydroquinone sulfates (Wakimoto et al., 1999), geranylfarnesylacetone (Ponomarenko et al., 1998), and sarcotragins A and B (Shin et al., 2001). In our previous study on the cytotoxic compounds of two sponges of the genus Sarcotragus, 33 cytotoxic terpenoids, three cyclitols, a trisoxazole macrolide, and three indole alkaloids were reported (Liu et al., 2001, 2002a,b, 2003, 2005, 2006). 3. Present study The frozen sponge (7 kg) was extracted with MeOH at room tempearature. The MeOH extract of the sponge displayed moderate cytotoxicities against five human tumor cell lines (ED50 values for A549, SK-OV-3, SK-MEL-2, XF498, and HCT15 were 19.0, 20.3, 11.8, 15.5, and 12.6 mg/mL, respectively) and showed toxicity to brine shrimp larvae (LD50, 93 mg/mL). The MeOH extract was partitioned between water and CH2Cl2. The CH2Cl2 layer was * Corresponding author. Tel.: þ86 20 89023105; fax: þ86 20 84451672. E-mail address: [email protected] (Y. Liu). 0305-1978/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.bse.2006.06.003

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further partitioned between 90% methanol and n-hexane to yield 90% methanol (54 g) and n-hexane soluble (13 g) fractions. As described in our previous report (Liu et al., 2001), the 90% methanol fraction was subjected to ˚ 500/400 mesh), eluting with a solvent system reversed-phase flash column chromatography (YMC Gel ODS-A, 60 A of 25e0% H2O/MeOH, to afford 20 fractions (Fg1eFg20). These fractions were evaluated for activity in the brine shrimp assay, and fractions Fg6eFg9 were found active. Compounds 1 (5.0 mg) and 2 (2.2 mg) were obtained by purification of fraction Fg3 by ODS HPLC. Marine sponges of the order Dictyoceratida have frequently provided a large number of linear sesterterpenoids (Blunt et al., 2006 and Faulkner, 2002). In our continuing investigation, two pyrrolosesterterpenes (1 and 2) were isolated from the sponge Sarcotragus. Compounds 1 and 2 were identified by comparison of their spectral data (1H, 13C NMR and MS) with those previously reported by us, the compounds having been isolated from other species of the genus Sarcotragus (Liu et al., 2003).

OH R1

N

R2

O

COONa

O

1 R1 = H2, R2 = O 2 R1 = O, R2 = H2

Compound 1 was isolated as a light yellow solid. The molecular formula of 1 was established as C27H36NO6Na on the basis of FABMS data. The H-10 signal (d 4.01) displayed HMBC correlations to the signals of C-1 (d 53.1), C-4 (d 172.9), and C-20 carboxylic carbon (d 176.3). Further evidence for the location of the C-4 carbonyl group was obtained from its HMBC correlation with the H-5 methylene proton signal at d 2.22. The 1H and 13C NMR data of the tetronic acid terminus of 1 exhibited typical chemical shifts for H-21 (d 4.34), H-20 (d 2.60, 2.14), H-17 (d 5.23), H-25 (d 1.54), C-22 (d 187.1), C-24 (d 193.2), and C-23 (d 88.4), which were very close to those of (21R)-isomers such as episarcotins. Thus, the configuration at C-21 was proposed as R on the basis of NMR data. The configuration at C-13 was assumed to be the same as those of epi-sarcotrines (Liu et al., 2001, 2002a, 2003). Compound 2 was isolated as a yellow oil. In the FABMS, compound 2 showed a [M þ Na]þ ion at m/z 516, indicating the same molecular mass as 1. The 1H and 13C NMR spectral data of 2 showed a close homology to those of 1. The singlet methylene proton at d 4.12, which was correlated to the carbon signal at d 55.8, was assigned to H-4. The H-4 signal showed HMBC correlation to the methylene carbon signals at dC 47.0 (C-10 ) and 29.8 (C-5). The H-5 signal showed long-range coupling to the signal at dC 55.8 (C-4) instead of the carbonyl carbon signal. Therefore, 2 can be differentiated from 1 as carrying a b-substituted lactam ring instead of the R-substituted one. A (21R)-configuration was proposed on the basis of 1H and 13C NMR spectral data. The configuration at C-13 was assumed to be the same as those of epi-sarcotrines (Liu et al., 2001, 2002a, 2003).

3.1. Sarcotrine E (1) Light yellow oil. 1H NMR (500 MHz, CD3OD) d 4.05 (2H, br s, H-1), 6.83 (1H, br s, H-2), 2.22 (2H, t, J ¼ 7.5 Hz, H-5), 1.69 (2H, m, H-6), 2.08 (2H, t, J ¼ 7.0 Hz, H-7), 1.72 (3H, s, H-9), 5.79 (1H, d, J ¼ 11.0 Hz, H-10), 6.19 (1H, dd, J ¼ 15.0, 11.0 Hz, H-11), 5.39 (1H, dd, J ¼ 15.0, 8.0 Hz, H-12), 2.15 (1H, m, H-13), 0.98 (3H, d, J ¼ 6.0 Hz, H-14), 1.31 (2H, m, H-15), 2.01 (2H, q, J ¼ 8.0 Hz, H-16), 5.23 (1H, t, J ¼ 7.0 Hz, H-17), 1.76 (3H, s, H-19), 2.60 (1H, dd, J ¼ 14.0, 2.0 Hz, H-20a), 2.26 (1H, dd, J ¼ 14.0, 10.0 Hz, H-20b), 4.34 (1H, dd, J ¼ 10.0, 2.0 Hz, H-21), 1.54 (3H, s, H-25), 4.01 (2H, s, H-10 ). 13C NMR (50 MHz, CD3OD) d 53.1 (C-1), 137.7 (C-2), 140.0 (C-3), 172.9 (C-4), 26.3 (C-5), 27.1 (C-6), 40.5 (C-7), 136.5 (C-8), 16.5 (C-9), 126.3 (C-10), 126.7 (C-11), 139.4 (C-12), 38.0 (C-13), 21.2 (C-14), 38.5 (C-15), 26.9 (C-16), 128.9 (C-17), 132.6 (C-18), 24.3 (C-19), 36.1 (C-20), 81.4 (C-21), 187.1 (C-22), 88.4 (C-23), 193.2 (C-24), 6.0 (C-25), 47.1 (C-10 ), 176.3 (C-20 ). FABMS m/z 516 [M þ Na]þ.

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3.2. Isosarcotrine E (2) Light yellow oil. 1H NMR (500 MHz, CD3OD) d 5.81 (1H, br s, H-2), 4.12 (2H, d, J ¼ 1.5 Hz, H-4), 2.38 (2H, t, J ¼ 7.5 Hz, H-5), 1.68 (2H, m, H-6), 2.06 (2H, t, J ¼ 7.0 Hz, H-7), 1.70 (3H, s, H-9), 5.78 (1H, d, J ¼ 11.0 Hz, H-10), 6.18 (1H, dd, J ¼ 15.0, 11.0 Hz, H-11), 5.40 (1H, dd, J ¼ 15.0, 8.0 Hz, H-12), 2.12 (1H, m, H-13), 0.98 (3H, d, J ¼ 7.0 Hz, H-14), 1.32 (2H, m, H-15), 2.00 (2H, q, J ¼ 8.0 Hz, H-16), 5.23 (1H, t, J ¼ 7.0 Hz, H-17), 1.76 (3H, s, H-19), 2.58 (1H, dd, J ¼ 14.0, 2.5 Hz, H-20a), 2.14 (1H, dd, J ¼ 14.0, 10.0 Hz, H-20b), 4.34 (1H, dd, J ¼ 10.0, 2.5 Hz, H-21), 1.54 (3H, s, H-25), 3.97 (2H, s, H-10 ). 13C NMR (50 MHz, CD3OD) d 173.8 (C-1), 121.8 (C-2), 136.5 (C-3), 55.8 (C-4), 29.8 (C-5), 27.0 (C-6), 40.2 (C-7), 136.0 (C-8), 16.4 (C-9), 126.5 (C-10), 127.0 (C-11), 140.2 (C-12), 38.0 (C-13), 21.5 (C-14), 38.5 (C-15), 26.8 (C-16), 128.9 (C-17), 132.7 (C-18), 24.3 (C-19), 36.1 (C-20), 81.4 (C-21), 183.6 (C-22), 88.0 (C-23), 193.2 (C-24), 6.0 (C-25), 47.0 (C-10 ), 174.0 (C-20 ). FABMS m/z 516 [M þ Na]þ. 4. Chemotaxonomic significance To the best of our knowledge, linear pyrrolosesterterpenes have been reported from only three species of the genus Sarcotragus (Shin et al., 2001 and Liu et al., 2002a, 2003), although pyrrolosesterterpenes, such as palinurines A and B, had been artificially generated from a furanosesterterpene through fungal biotransformation (Sayed et al., 1999). From a chemical point of view, the species of the genus Sarcotragus have been the source of pyrrolosesterterpenes. Consistent, reliable production and the ease with which these pyrrolosesterterpenes can be visualized using Dragendorff’s reagent during TLC profiling, make them important chemotaxonomic markers for Sarcotragus sp. Taxonomy based on morphological characters of Porifera is relatively difficult compared with other invertebrate phyla. The degree of inconsistency found prevents the use of chemical data as a single tool to solve taxonomic classification. However, multidisciplinary approaches that combine histological, ecological, and/or chemical data with sponge morphology have proven useful to differentiate between closely related species. Species of the genus Sarcotragus are frequently difficult to differentiate due to their morphological characteristics. Thus, the use of additional criteria may provide valuable clues for taxonomic classification. Acknowledgments Our thanks are due to C. J. Sim of Hannam University for the identification of the sponge. This study was supported by a grant from Marine Bio 21 the Ministry of Maritime Affairs and Fisheries, Korea and the grant from Hundred Talents Project of Chinese Academy of Sciences. References Barrow, C.J., Blunt, J.W., Munro, M.H.G., Perry, N.B., 1988. J. Nat. Prod. 51, 275. Blunt, J.W., Copp, B.R., Munro, M.H.G., Northcote, P.T., Prinsep, M.R., 2006. Nat. Prod. Rep. 23, 26, and earlier reviews cited therein. Faulkner, D.J., 2002. Nat. Prod. Rep. 1, 1, and earlier reviews cited therein. Liu, Y., Bae, B.H., Alam, N., Hong, J., Sim, C.J., Lee, C.-O., Im, K.S., Jung, J.H., 2001. J. Nat. Prod. 64, 1301. Liu, Y., Hong, J., Lee, C.-O., Im, K.S., Kim, N.D., Choi, J.S., Jung, J.H., 2002a. J. Nat. Prod. 65, 1307. Liu, Y., Lee, C.-O., Hong, J., Jung, J.H., 2002b. Bull. Korean Chem. Soc. 23, 1467. Liu, Y., Mansoor, T.A., Hong, J., Lee, C.-O., Sim, C.J., Im, K.S., Jung, J.H., 2003. J. Nat. Prod. 11, 1451. Liu, Y., Shinde, P.B., Hong, J., Lee, C.-O., Im, K.S., Jung, J.H., 2005. Nat. Prod. Sci. 11, 50. Liu, Y., Jung, J.H., Zhang, S., 2006. Biochem. Syst. Ecol. 34, 453. Perry, N.B., Battershill, C.N., Blunt, J.W., Fenwick, G.D., Munro, M.H.G., Bergquist, P.R., 1987. Biochem. Syst. Ecol. 15, 373. Ponomarenko, L.P., Makareva, T.N., Stonik, V.A., 1998. Russ. Chem. Bull. 47, 2017. Sayed, K.A.E., Mayer, A.M.S., Kelly, M., Hamann, M.T., 1999. J. Org. Chem. 64, 9258. Shin, J., Seo, Y., Cho, K.W., Rho, J.R., Sim, C.J., 2001. Tetrahedron Lett. 42, 3005. Stonik, V.A., Makarieva, T.N., Dmitrenok, A.S., 1992. J. Nat. Prod. 55, 1256. Wakimoto, T., Maruyama, A., Matsunaga, S., Fusetani, N., Shinoda, K., Murphy, P.T., 1999. Bioorg. Med. Chem. Lett. 9, 727.