Download PDF
Synlett 2011(3): 425-429  
DOI: 10.1055/s-0030-1259511
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Design and Synthesis of Brazilin-Like Compounds

Chengxue Pan, Xianghui Zeng, Yifu Guan, Xiangliu Jiang, Liang Li, Hongbin Zhang*
Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, P. R. of China
Fax: +86(871)5035538; e-Mail: zhanghb@ynu.edu.cn;
Further Information

Publication History

Received 20 October 2010
Publication Date:
25 January 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A general and flexible synthetic route, which leads to the synthesis of brazilin-like compounds, was developed. The aza-­brazilin derivatives show strong anticancer activities in MTT assay towards a number of human cancer cell lines including HT29, A549, HL60, and K562.

Key words

synthetic strategy - bioactive derivatives - anticancer - natural-product-like - brazilin

    References and Notes

  • 1a Robinson R. Bull. Soc. Chim. Fr.  1958,  125 
    Google Scholar
  • 1b Craig JC. Naik AR. Pratt R. Johnson E. Bhacca NS.
    J. Org. Chem.  1965,  30:  1573 
    Google Scholar
  • 1c Yang BO. Ke CQ. He ZS. Yang YP. Ye Y. Tetrahedron Lett.  2002,  43:  1731 
    Google Scholar
  • 2 Moon C.-K. Lee S.-H. Chung J.-H. Kim S.-G. Chung M.-K. Moon C.-H. Arch. Pharm. Res.  1990,  13:  355 
    CrossrefGoogle Scholar
  • 3 Hwang GS. Kim JY. Chang TS. Jeon SD. So DS. Moon CK. Arch. Pharm. Res.  1998,  21:  774 
    CrossrefGoogle Scholar
  • 4a Choi S.-Y. Yang K.-M. Jeon S.-D. Kim J.-H. Khil L.-Y. Chang T.-S. Moon C.-K. Planta Med.  1997,  63:  405 
    Google Scholar
  • 4b Mok MS. Jeon SD. Yang KM. So DS. Moon CK. Arch. Pharm. Res.  1998,  21:  769 
    Google Scholar
  • 5a Bae IK. Min HY. Han AR. Seo EK. Lee SK. Eur. J. Pharmacol.  2005,  513:  237 
    Google Scholar
  • 5b Sasaki Y. Hosokawa T. Nagai M. Nagumo S. Biol. Pharm. Bull.  2007,  30:  193 
    Google Scholar
  • 5c Hu C.-M. Liu Y.-H. Cheah K.-P. Li J.-S. Lam C.-SK. Yu W.-Y. Choy C.-S. J. Ethnopharm.  2009,  121:  79 
    Google Scholar
  • 6a Choi B.-M. Lee J.-A. Gao SS. Eun SY. Kim Y.-S. Ryu S.-Y. Choi Y.-H. Park R. Kwon DY. Kim B.-R. BioFactors  2007,  30:  149 
    Google Scholar
  • 6b Choi B.-M. Kim B.-R. Eur. J. Pharm.  2008,  580:  12 
    Google Scholar
  • 7a Chin RL, and Tolman AC. inventors; WO  0,193,864. 
  • 7b Mar W. Lee H.-T. Je K.-H. Choi H.-Y. Seo E.-K. Arch. Pharm. Res.  2003,  26:  147 
    Google Scholar
  • 7c Yen C.-T. Nakagawa-Goto K. Hwang T.-L. Wu P.-C. Morris-Natschke S.-L. Lai W.-C. Bastow KF. Chang F.-R. Wu Y.-C. Lee K.-H. Bioorg. Med. Chem. Lett.  2010,  20:  1037 
    Google Scholar
  • 8 Lee K.-H. J. Nat. Prod.  2010,  73:  500 
    CrossrefGoogle Scholar
  • 9 Tietze LF. Bell HP. Chandrasekhar S. Angew. Chem. Int. Ed.  2003,  42:  3996 
    CrossrefPubMedGoogle Scholar
  • 11 Christoffers J. Werner T. Unger S. Frey W. Eur. J. Org. Chem.  2003,  425 
    Google Scholar
10

CCDC804781 (for compound 4a) and CCDC804782 (for compound 4d) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

12

Representative Brazilin-Like Compounds
Lactone analogue 4e: pale red syrup. ¹H NMR (300 MHz, CDCl3): δ = 7.02 (1 H, d, J = 7.5 Hz), 6.70-6.86 (4 H, m), 4.15 (1 H, s), 3.84 (3 H, s), 3.81 (3 H, s), 3.77 (3 H, s), 3.34 (1 H, d, J = 15.3 Hz), 3.04-3.13 (2 H, m), 2.84 (1 H, d, J = 15.6 Hz) ppm. ¹³C NMR (75 MHz, CDCl3): δ = 148.41, 148.12, 146.88, 137.37, 133.69, 130.87, 122.96, 121.67, 117.82, 108.72, 77.83, 56.10, 55.48, 52.51, 48.07, 42.13 ppm. MS (EI): m/z (%) = 328 (25) [M+ + 1], 327 (100) [M+], 309 (23), 308 (86), 294 (32), 278 (9), 250 (4), 239 (4), 220 (4), 208 (4), 191 (4), 176 (58), 151 (65), 133 (13), 107 (12). HRMS: m/z calcd for C19H21NO4 [M]+: 327.1471; found: 327.1479.

13

The cytotoxicity assay was carried out on four cell lines (K562, A549, HT-29, and HL60). Cells were cultured at 37 ˚C under a humidified atmosphere of 5% CO2 in RPMI 1640 medium supplemented with 10% fetal serum and dispersed in replicate 96-well plates. Compounds were then added. After 48 h exposure to the compounds, cells viability were determined by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-
tetrazolium bromide] (MTT) cytotoxicity assay by measur-ing the absorbance at λ = 570 nm with a microplate spectrophotometer. Each test was performed in triplicate. Cisplatin (DDP) was used as the reference drug.