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Synlett 2011(3): 378-382  
DOI: 10.1055/s-0030-1259330
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Access to the Bicyclic Core of Isatisine, and an Investigation of Its Antibacterial Activity

Christopher J. Matthews, Mark G. Moloney*, Amber L. Thompson, Hanna Winiarska, Henry T. Winney
Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK
Fax: +44(1865)285002; e-Mail: mark.moloney@chem.ox.ac.uk;
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Publikationsverlauf

Received 15 November 2010
Publikationsdatum:
19. Januar 2011 (online)

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Abstract

A chemoselective Dieckmann ring closure using an oxazolidine derived from serine may be used to generate a tetramic acid, the further manipulation of which by reduction and ring closure leads to the bicyclic core of isatisine; depending on the nature of the ring closing electrophile, different diastereomers are obtained. None of the compounds from this sequence exhibited activity against S. aureus but several showed activity against E. coli.

Key words

heterocycles - natural products - cyclisation - antibiotics - lactams

    References and Notes

  • 1a Kotra LP. Golemi D. Vakulenko S. Mobashery S. Chem. Ind. (London)  2000,  341 
    Google Scholar
  • 1b Niccolai D. Tarsi L. Thomas RJ. Chem. Commun.  1997,  2333 
    Google Scholar
  • 1c Peet NP. Drug Discovery Today  2010,  15:  583 
    Google Scholar
  • 2a Morel C. Mossialos E. Br. Med. J.  2010,  340:  1115 
    Google Scholar
  • 2b So AD. Gupta N. Cars O. Br. Med. J.  2010,  340:  1091 
    Google Scholar
  • 3 Newman DJ. Cragg GM. J. Nat. Prod.  2007,  70:  461 
    CrossrefPubMedGoogle Scholar
  • 4a Danishefsky S. Nat. Prod. Rep.  2010,  27:  1114 
    Google Scholar
  • 4b Cheng CC. Shipps GW. Yang Z. Sun B. Kawahata N. Soucy KA. Soriano A. Orth P. Xiao L. Mann P. Black T. Bioorg. Med. Chem. Lett.  2009,  19:  6507 
    Google Scholar
  • 4c Galloway WRJD. Bender A. Welch M. Spring DR. Chem. Commun.  2009,  2446 
    Google Scholar
  • 4d Cordier C. Morton D. Murrison S. Nelson A. O’Leary-Steele C. Nat. Prod. Rep.  2008,  25:  719 
    Google Scholar
  • 4e Newman DJ. J. Med. Chem.  2008,  51:  2589 
    Google Scholar
  • 5a vonNussbaum F. Brands M. Hinzen B. Weigand S. Habich D. Angew. Chem. Int. Ed.  2006,  45:  5072 
    Google Scholar
  • 5b Nören-Müller A. Reis-Correa I. Prinz H. Rosenbaum C. Saxena K. Schwalbe HJ. Vestweber D. Cagna G. Schunk S. Schwarz O. Schiewe H. Waldmann H. Proc. Natl. Acad. Sci. U.S.A.  2006,  103:  10606 
    Google Scholar
  • 5c Baltz RH. J. Ind. Microbiol. Biotechnol.  2006,  33:  507 
    Google Scholar
  • 5d Gullo VP. McAlpine J. Lam KS. Baker D. Petersen F. J. Ind. Microbiol. Biotechnol.  2006,  33:  523 
    Google Scholar
  • 5e Koch MA. Waldmann H. Drug. Discovery Today  2005,  10:  471 
    Google Scholar
  • 5f Koehn FE. Carter GT. Nat. Rev. Drug Discovery  2005,  4:  206 
    Google Scholar
  • 5g Shang S. Tan DS. Curr. Opin. Chem. Biol.  2005,  9:  248 
    Google Scholar
  • 5h Ganesan A. Curr. Opin. Biotechnol.  2004,  15:  584 
    Google Scholar
  • 5i Njardarson JT. Gaul C. Shan D. Huang X.-Y. Danishefsky SJ. J. Am. Chem. Soc.  2004,  126:  1038 
    Google Scholar
  • 5j Rouhi AM. Chem. Eng. News  2003,  81:  77 
    Google Scholar
  • 5k Breinbauer RB. Vetter IR. Waldmann H. Angew. Chem. Int. Ed.  2002,  41:  2878 
    Google Scholar
  • 5l Hemkens PHH. Ottenheijm HCJ. Rees DC. Tetrahedron  1997,  53:  5643 
    Google Scholar
  • 6 O’Shea R. Moser HE. J. Med. Chem.  2008,  51:  2871 
    CrossrefGoogle Scholar
  • 7a Hajduk PJ. J. Med. Chem.  2006,  49:  6972 
    Google Scholar
  • 7b Rees DC. Congreve M. Murray CW. Carr R. Nat. Rev. Drug Discovery  2004,  3:  660 
    Google Scholar
  • 8a Balamurugan R. Dekkerab FJ. Waldmann H. Mol. BioSyst.  2005,  1:  36 
    Google Scholar
  • 8b Koch MA. Wittenberg LO. Basu S. Jeyaraj DA. Gourzoulidou E. Reinecke K. Odermatt A. Waldmann H. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  16721 
    Google Scholar
  • 9 Zhou J. Xie G. Yan X. Traditional Chinese Medicines   Ashgate; England: 2004. 
    Google Scholar
  • 10 Anwar M. Cowley AR. Moloney MG. Tetrahedron: Asymmetry  2010,  21:  1758 
    CrossrefGoogle Scholar
  • 11 Jeong Y.-C. Moloney MG. Synlett  2009,  2487 
    Artikel in Thieme ConnectGoogle Scholar
  • 12a Chandan N. Moloney MG. Org. Biomol. Chem.  2008,  6:  3664 
    Google Scholar
  • 12b Hill T. Kocis P. Moloney MG. Tetrahedron Lett.  2006,  47:  1461 
    Google Scholar
  • 13 Liu J.-F. Jiang Z.-Y. Wang R.-R. Zheng Y.-T. Chen J.-J. Zhang X.-M. Ma Y.-B. Org. Lett.  2007,  9:  4127 
    CrossrefGoogle Scholar
  • 15 Karadeolian A. Kerr MA. Angew. Chem. Int. Ed.  2010,  49:  1133 
    CrossrefGoogle Scholar
  • 16 Andrews MD. Brewster AG. Moloney MG. Synlett  1996,  612 
    Artikel in Thieme ConnectGoogle Scholar
  • 17 Andrews MD. Brewster AG. Crapnell KM. Ibbett AJ. Jones T. Moloney MG. Prout K. Watkin D. J. Chem. Soc., Perkin Trans. 1  1998,  223 
    Google Scholar
  • 19 Galeotti N. Poncet J. Chiche L. Jouin P. J. Org. Chem.  1993,  58:  5370 
    CrossrefGoogle Scholar
  • 20 Andrews MD. Brewster AG. Moloney MG. J. Chem. Soc., Perkin Trans. 1  2002,  80 
    Google Scholar
  • 21 Ling T. Macherla VR. Manam RR. McArthur KA. Potts BCM. Org. Lett.  2007,  9:  2289 
    CrossrefPubMedGoogle Scholar
  • 22 Cottrell IF. Cowley AR. Croft LJ. Hymns L. Moloney MG. Nettleton EJ. Smithies HK. Thompson AL. Tetrahedron  2009,  65:  2537 
    CrossrefGoogle Scholar
  • 23 Cottrell IF. Moloney MG. Smithies HK. Tetrahedron Lett.  2009,  50:  1097 
    CrossrefGoogle Scholar
  • 24 Moloney MG. Nettleton E. Smithies K. Tetrahedron Lett.  2002,  43:  907 
    CrossrefGoogle Scholar
  • 25a Moloney MG. Main Group Met. Chem.  2001,  24:  653 
    Google Scholar
  • 25b Buston JEH. Claridge TDW. Moloney MG.
    J. Chem. Soc., Perkin Trans. 2  1995,  639 
    Google Scholar
  • 26 Corey EJ. Reichard GA. J. Am. Chem. Soc.  1992,  114:  10677 
    CrossrefGoogle Scholar
  • 29 Ferrara P. Apostolakis J. Caflisch A. Proteins: Struct., Funct., Bioinf.  2002,  46:  24 
    CrossrefGoogle Scholar
  • 30a Padrón JA. Carrasco R. Pellón RF. J. Pharm. Pharmaceut. Sci.  2002,  5:  258 
    Google Scholar
  • 30b Ghose AK. Crippen GM. J. Chem. Inf. Comput. Sci.  1987,  27:  21 
    Google Scholar
  • 30c Viswanadhan VN. Ghose AK. Reyankar GR. Robins RK. J. Chem. Inf. Comput. Sci.  1989,  29:  163 
    Google Scholar
  • 31 Ertl P. Rohde B. Selzer P. J. Med. Chem.  2000,  43:  3714 
    CrossrefGoogle Scholar
  • 32 Ertl P. ‘Polar Surface Area’, in Molecular Drug Properties   Mannhold R. Wiley-VCH; Weinheim: 2007.  p.111-126  
    Google Scholar
  • 33 Reymond J.-L. van Deursen R. Blum LC. Ruddigkeit L. MedChemComm  2010,  1:  30 
    CrossrefGoogle Scholar
  • 34 Hajduk PJ. Greer J. Nat. Rev. Drug Discovery  2007,  211 
    Google Scholar
  • 35 Anwar M. Moloney MG. Tetrahedron Lett.  2007,  48:  7259 
    CrossrefGoogle Scholar
  • 36a Bagwell CL. Moloney MG. Thompson AL. Bioorg. Med. Chem. Lett.  2008,  18:  4081 
    Google Scholar
  • 36b Bagwell CL. Moloney MG. Yaqoob M. Bioorg. Med. Chem. Lett.  2010,  20:  2090 
    Google Scholar
  • 37 Cosier J. Glazer AM. J. Appl. Crystallogr.  1986,  19:  105 
    CrossrefGoogle Scholar
  • 38 Otwinowski Z. Minor W. Methods Enzymol.  1997,  276:  307 
    PubMedGoogle Scholar
  • 39 Altomare A. Cascarano G. Giacovazzo G. Guagliardi A. Burla MC. Polidori G. Camalli M. J. Appl. Crystallogr.  1994,  27:  435 
    CrossrefGoogle Scholar
  • 40 Betteridge PW. Carruthers JR. Cooper RI. Prout K. Watkin DJ. J. Appl. Crystallogr.  2003,  36:  1487 
    CrossrefGoogle Scholar
  • 41a Flack HD. Acta Crystallogr., Sect. A  1983,  39:  876 
    Google Scholar
  • 41b Flack HD. Bernardinelli G. J. Appl. Crystallogr.  2000,  33:  1143 
    Google Scholar
  • 42 Hooft RWW. Straver LH. Spek AL. J. Appl. Crystallogr.  2008,  41:  96 
    CrossrefGoogle Scholar
  • 43a Thompson AL. Watkin DJ. Gal ZA. Jones L. Hollinshead J. Jenkinson SF. Fleet GWJ. Nash RJ. Acta Crystallogr., Sect. C  2008,  64:  o649 
    Google Scholar
  • 43b Thompson AL. Watkin DJ. Tetrahedron: Asymmetry  2009,  20:  712 
    Google Scholar
  • 44a Smith B. Warren SC. Newton GGF. Abraham EP. Biochem. J.  1967,  103:  877 
    Google Scholar
  • 44b Baldwin JE. Coates JB. Halpern J. Moloney MG. Pratt AJ. Biochem. J.  1989,  261:  197 
    Google Scholar
  • 44c Baldwin JE. Pratt AJ. Moloney MG. Tetrahedron  1987,  43:  2565 
    Google Scholar
14

Communication from Shanghai Innovative Research Center of Traditional Chinese Medicine.

18

The diffraction data for 7b and 15a were collected at 150 K³7 using an Enraf-Nonius KCCD diffractometer.³8 Structures were solved using SIR92,³9 and refined using the CRYSTALS software suite40 as per the supplementary information (CIF file). The Flack x parameter 4¹ for 7b refined to -0.2 (8), however analysis of the Bijvoet pairs gave a Hooft y parameter4² of 0.0(3) giving a 99.2% probability that the structure is of the correct handedness (assuming full enantiopurity).4³ In the absence of a strong anomalous signal, the Friedel pairs were merged for the final refinement. The Flack x parameter for 15a refined to -0.02 (3). Crystallographic data (excluding structure factors) have been deposited with the Cambridge Crystallographic Data Centre [CCDC 800835 (7b), CCDC 800836 (15a)] and copies of these data can be obtained via www.ccdc.cam.ac.uk/data_request/cif.

27

Bioassay of Compounds:44 Microbiological assays were performed by the hole-plate method with the test organism Staphylococcus aureus N.C.T.C. 6571 or E. coli X580. Solutions (100 mL) of the compounds to be tested (4 mg/mL) were loaded into wells in bioassay plates, and incubated overnight at 37 ˚C. The diameters of the resultant inhibition zones were measured (±1 mm).

28

Marvin was used for drawing, displaying and structure property prediction and calculation (ClogD7.4, PSA, MSA and CMR calculations), Marvin 5.2.1, 2009, ChemAxon (http://www.chemaxon.com).