Abstract
A series of heteronemin-related antitubercular scalaranes, both from natural products and from chemical derivatization, were subjected to structure-activity investigations. Based on the activity profile, three main regions; i.e., the substituted groups hovering over C-19/C-18 and furan moiety, the functionalities in the vicinity of C-16 and the right-hand side of ring D, and the substituted groups on C-12, were speculated as the areas influencing the antitubercular activity of the scalaranes. The results suggested the promising possibility for the further investigation towards the modes of actions and/or target sites of the compounds.
Conference
International Conference on Biodiversity and Natural Products (ICOB-6 & ISCNP-26), International Conference on Biodiversity, International Symposium on the Chemistry of Natural Products, ICOB, ISCNP, Biodiversity, Natural Products, Charlottetown, Prince Edward Island, Canada, 2008-07-13–2008-07-18
References
1. (a) doi:10.1021/np50048a012, P. Crews, P. Bescansa. J. Nat. Prod. 49, 1041 (1986);Search in Google Scholar
1. (b) Y. Doi, H. Shigamori, M. Ishibashi, F. Mozobe, A. Kawashima, S. Nakaike, J. Kobayashi. Chem. Pharm. Bull. 41, 2190 (1993);10.1248/cpb.41.2190Search in Google Scholar PubMed
1. (c) M. Kobayashi, T. Okamoto, K. Hayashi, N. Yokoyama, T. Sasaki, I. Kitagawa. Chem. Pharm. Bull. 42, 265 (1994);10.1248/cpb.42.265Search in Google Scholar PubMed
1. (d) doi:10.1021/np960130e, G. Ryu, S. Matsunaga, N. Fusetani. J. Nat. Prod. 59, 515 (1996);Search in Google Scholar
1. (e) doi:10.1080/13880200490886120, V. Ledroit, C. Debitus, F. Ausseil, R. Raux, J. Menou, B. T. Hill. Pharm. Biol. 42, 454 (2004).Search in Google Scholar
2. (a) doi:10.1021/np50062a012, P. Karuso, R. C. Cambie, B. F. Bowden, P. R. Berquist. J. Nat. Prod. 52, 2889 (1989);Search in Google Scholar
2. (b) doi:10.1016/j.tet.2006.03.075, C. J. Hernandez-Guerrero, E. Zubia, M. J. Ortega, J. L. Carballo. Tetrahedron 62, 5392 (2006);Search in Google Scholar
2. (c) doi:10.1021/np060244i, M. J. Somerville, J. N. A. Hooper, M. J. Garson. J. Nat. Prod. 69, 1587 (2006).Search in Google Scholar
3. (a) doi:10.1021/np50074a002, C. B. Rao, R. S. H. S. N. Kalidindi, G. Trimurtulu, D. V. Rao. J. Nat. Prod. 54, 364 (1991);Search in Google Scholar
3. (b) doi:10.1021/np070020f, H. Li, T. Amagata, K. Tenney, P. Crews. J. Nat. Prod. 70, 802 (2007).Search in Google Scholar
4. doi:10.1021/np040103l, J. Rho, H. Lee, H. J. Shin, J. Ahn, J. Kim, C. J. Sim, J. Shin. J. Nat. Prod. 67, 1748 (2004).Search in Google Scholar
5. doi:10.1016/j.bmcl.2006.07.079, S. Nam, H. Ko, M. Shin, J. Ham, J. Chin, Y. Kim, H. Kim, K. Shin, H. Choi, H. Kang. Bioorg. Med. Chem. Lett. 16, 5398 (2006).Search in Google Scholar
6. doi:10.1021/np9900932, A. Fontana, P. Cavaliere, N. Ungur, L. D'Souza, P. S. Parameswaram, G. Cimino. J. Nat. Prod. 62, 1367 (1999).Search in Google Scholar
7. (a) doi:10.1016/S0040-4039(00)91753-2, R. Kazlauskas, P. T. Murphy, R. J. Quinn, R. J. Wells. Tetrahedron Lett. 30, 2631 (1976);Search in Google Scholar
7. (b) doi:10.1016/0040-4020(77)88036-8, Y. Kashman, A. Rudi. Tetrahedron 33, 2997 (1977).Search in Google Scholar
8. doi:10.1016/S0040-4020(99)01093-5, K. A. El Sayed, P. Bartyzel, X. Shen, T. L. Perry, J. K. Zjawiony, M. T. Hamann. Tetrahedron 56, 949 (2000).Search in Google Scholar
9. doi:10.1021/np0498354, S. Wonganuchitmeta, S. Yuenyongsawad, N. Keawpradub, A. Plubrukarn. J. Nat. Prod. 67, 1767 (2004).Search in Google Scholar
10. The sponge was identified by Dr. Somchai Bussarawit of Phuket Marine Biology Center. The voucher specimen (PMBC 24608) is deposited at Phuket Marine Biology Center, Phuket, Thailand.Search in Google Scholar
11. The sponge was extracted in MeOH, and the crude MeOH-extract was partitioned to yield a hexane-extract, which was subjected to a series of chromatographic separation (SiO2, hexane:EtOAc:acetone 7:2:1; then SiO2, gradient hexane:EtOAc 7:3 1:1) to yield 6 (5 mg). 12epi-deacetyl-19α-acetoxy-20α-methoxyscalaran (6). White solid; [α]D +7.1 (c 0.21, CHCl3); UV (MeOH) λmax (log ε) 208 (4.47), 218 (4.45) nm; IR (neat) νmax 3444, 1734 cm1; 1H NMR (500 MHz, CDCl3) δ 6.45 (d, J = 3.0 Hz; H-19), 5.79 (dd, J = 6.5, 3.0 Hz; H-16), 5.09 (s; H-20), 3.38 (d, J = 12.0, 4.5 Hz; H-12), 3.32 (s, 3H; 20-OCH3), 2.81 (t, J = 3.0 Hz; H-18), 2.08 (m; H15a), 2.04 (s, 3H; 19-OCOCH3), 1.95 (m; H-15b), 1.64 (m; H-11a), 1.56 (m; H-1a), 1.51 (m; H-7a), 1.45 (m; H-2a), 1.40 (m; H-6a), 1.33 (m; H-11b), 1.29 (m,; H-2b), 1.26 (m; H-6b), 1.24 (m; H-3a), 1.15 (dd, J = 11.0, 5.5 Hz; H-14), 1.07 (td, J = 13.0, 3.5 Hz; H-3b), 0.86 (m; H9), 0.85 (m; H-7b), 0.83 (s, 3H; H-24), 0.81 (m; H-1b), 0.78 (s, 6H; H-21 & H-23), 0.74 (s, 3H; H22), 0.72 (dd, J = 14.0, 2.0 Hz; H-5), 0.69 (s, 3H; H-26); 13C NMR (125 MHz, CDCl3) δ 171.0 (19-OCOCH3), 135.8 (C-17), 121.8 (C-16), 104.6 (C-20), 99.6 (C-19), 80.5 (C-12), 58.6 (C-9), 56.8 (C-18), 56.4 (C-5), 54.6 (20-OCH3), 53.1 (C-14), 42.0 (C-7), 41.3 (C-3), 39.9 (C-1), 39.2 (C-13), 37.5 (C-10), 37.3 (C-8), 33.2 (C-21), 33.3 (C-4), 27.6 (C-11), 22.4 (C-15), 21.3 (C-22), 21.3 (19-OCOCH3), 18.5 (C-6), 18.0 (C-2), 17.3 (C-24), 16.5 (C-23), 8.8 (C-25); HR-ESIMS m/z [M+Na]+ 483.3071 (calcd for C28H44O5Na 483.3087).Search in Google Scholar
12. doi:10.1021/jo00380a025, D. Askin, C. Angst, S. Danishefsky. J. Org. Chem. 52, 622 (1987).Search in Google Scholar
13. doi:10.1021/np040087s, M. Gavagnin, E. Mollo, T. Docimo, Y. Guo, G. Cimino. J. Nat. Prod. 67, 2104 (2004).Search in Google Scholar
14. doi:10.1021/jo00250a008, M. E. Kuenhe, W. G. Bornmann, W. H. Parsons, T. D. Spitzer, J. F. Blount, J. Zubieta. J. Org. Chem. 53, 3439 (1988).Search in Google Scholar
15. L. A. Collins, S. G. Franzblau. Antimicrob. Agents Chemother. 41, 1004 (1997).Search in Google Scholar
16. doi:10.1093/jnci/82.13.1107, P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J. T. Warren, H. Bokesch, S. Kenney, M. R. Boyd. J. Natl. Cancer Inst. 82, 1108 (1990).Search in Google Scholar
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