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;
Weitere Informationen

Publikationsverlauf

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

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.

    References and Notes

  • 1a Kotra LP. Golemi D. Vakulenko S. Mobashery S. Chem. Ind. (London)  2000,  341 
  • 1b Niccolai D. Tarsi L. Thomas RJ. Chem. Commun.  1997,  2333 
  • 1c Peet NP. Drug Discovery Today  2010,  15:  583 
  • 2a Morel C. Mossialos E. Br. Med. J.  2010,  340:  1115 
  • 2b So AD. Gupta N. Cars O. Br. Med. J.  2010,  340:  1091 
  • 3 Newman DJ. Cragg GM. J. Nat. Prod.  2007,  70:  461 
  • 4a Danishefsky S. Nat. Prod. Rep.  2010,  27:  1114 
  • 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 
  • 4c Galloway WRJD. Bender A. Welch M. Spring DR. Chem. Commun.  2009,  2446 
  • 4d Cordier C. Morton D. Murrison S. Nelson A. O’Leary-Steele C. Nat. Prod. Rep.  2008,  25:  719 
  • 4e Newman DJ. J. Med. Chem.  2008,  51:  2589 
  • 5a vonNussbaum F. Brands M. Hinzen B. Weigand S. Habich D. Angew. Chem. Int. Ed.  2006,  45:  5072 
  • 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 
  • 5c Baltz RH. J. Ind. Microbiol. Biotechnol.  2006,  33:  507 
  • 5d Gullo VP. McAlpine J. Lam KS. Baker D. Petersen F. J. Ind. Microbiol. Biotechnol.  2006,  33:  523 
  • 5e Koch MA. Waldmann H. Drug. Discovery Today  2005,  10:  471 
  • 5f Koehn FE. Carter GT. Nat. Rev. Drug Discovery  2005,  4:  206 
  • 5g Shang S. Tan DS. Curr. Opin. Chem. Biol.  2005,  9:  248 
  • 5h Ganesan A. Curr. Opin. Biotechnol.  2004,  15:  584 
  • 5i Njardarson JT. Gaul C. Shan D. Huang X.-Y. Danishefsky SJ. J. Am. Chem. Soc.  2004,  126:  1038 
  • 5j Rouhi AM. Chem. Eng. News  2003,  81:  77 
  • 5k Breinbauer RB. Vetter IR. Waldmann H. Angew. Chem. Int. Ed.  2002,  41:  2878 
  • 5l Hemkens PHH. Ottenheijm HCJ. Rees DC. Tetrahedron  1997,  53:  5643 
  • 6 O’Shea R. Moser HE. J. Med. Chem.  2008,  51:  2871 
  • 7a Hajduk PJ. J. Med. Chem.  2006,  49:  6972 
  • 7b Rees DC. Congreve M. Murray CW. Carr R. Nat. Rev. Drug Discovery  2004,  3:  660 
  • 8a Balamurugan R. Dekkerab FJ. Waldmann H. Mol. BioSyst.  2005,  1:  36 
  • 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 
  • 9 Zhou J. Xie G. Yan X. Traditional Chinese Medicines   Ashgate; England: 2004. 
  • 10 Anwar M. Cowley AR. Moloney MG. Tetrahedron: Asymmetry  2010,  21:  1758 
  • 11 Jeong Y.-C. Moloney MG. Synlett  2009,  2487 
  • 12a Chandan N. Moloney MG. Org. Biomol. Chem.  2008,  6:  3664 
  • 12b Hill T. Kocis P. Moloney MG. Tetrahedron Lett.  2006,  47:  1461 
  • 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 
  • 15 Karadeolian A. Kerr MA. Angew. Chem. Int. Ed.  2010,  49:  1133 
  • 16 Andrews MD. Brewster AG. Moloney MG. Synlett  1996,  612 
  • 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 
  • 19 Galeotti N. Poncet J. Chiche L. Jouin P. J. Org. Chem.  1993,  58:  5370 
  • 20 Andrews MD. Brewster AG. Moloney MG. J. Chem. Soc., Perkin Trans. 1  2002,  80 
  • 21 Ling T. Macherla VR. Manam RR. McArthur KA. Potts BCM. Org. Lett.  2007,  9:  2289 
  • 22 Cottrell IF. Cowley AR. Croft LJ. Hymns L. Moloney MG. Nettleton EJ. Smithies HK. Thompson AL. Tetrahedron  2009,  65:  2537 
  • 23 Cottrell IF. Moloney MG. Smithies HK. Tetrahedron Lett.  2009,  50:  1097 
  • 24 Moloney MG. Nettleton E. Smithies K. Tetrahedron Lett.  2002,  43:  907 
  • 25a Moloney MG. Main Group Met. Chem.  2001,  24:  653 
  • 25b Buston JEH. Claridge TDW. Moloney MG.
    J. Chem. Soc., Perkin Trans. 2  1995,  639 
  • 26 Corey EJ. Reichard GA. J. Am. Chem. Soc.  1992,  114:  10677 
  • 29 Ferrara P. Apostolakis J. Caflisch A. Proteins: Struct., Funct., Bioinf.  2002,  46:  24 
  • 30a Padrón JA. Carrasco R. Pellón RF. J. Pharm. Pharmaceut. Sci.  2002,  5:  258 
  • 30b Ghose AK. Crippen GM. J. Chem. Inf. Comput. Sci.  1987,  27:  21 
  • 30c Viswanadhan VN. Ghose AK. Reyankar GR. Robins RK. J. Chem. Inf. Comput. Sci.  1989,  29:  163 
  • 31 Ertl P. Rohde B. Selzer P. J. Med. Chem.  2000,  43:  3714 
  • 32 Ertl P. ‘Polar Surface Area’, in Molecular Drug Properties   Mannhold R. Wiley-VCH; Weinheim: 2007.  p.111-126  
  • 33 Reymond J.-L. van Deursen R. Blum LC. Ruddigkeit L. MedChemComm  2010,  1:  30 
  • 34 Hajduk PJ. Greer J. Nat. Rev. Drug Discovery  2007,  211 
  • 35 Anwar M. Moloney MG. Tetrahedron Lett.  2007,  48:  7259 
  • 36a Bagwell CL. Moloney MG. Thompson AL. Bioorg. Med. Chem. Lett.  2008,  18:  4081 
  • 36b Bagwell CL. Moloney MG. Yaqoob M. Bioorg. Med. Chem. Lett.  2010,  20:  2090 
  • 37 Cosier J. Glazer AM. J. Appl. Crystallogr.  1986,  19:  105 
  • 38 Otwinowski Z. Minor W. Methods Enzymol.  1997,  276:  307 
  • 39 Altomare A. Cascarano G. Giacovazzo G. Guagliardi A. Burla MC. Polidori G. Camalli M. J. Appl. Crystallogr.  1994,  27:  435 
  • 40 Betteridge PW. Carruthers JR. Cooper RI. Prout K. Watkin DJ. J. Appl. Crystallogr.  2003,  36:  1487 
  • 41a Flack HD. Acta Crystallogr., Sect. A  1983,  39:  876 
  • 41b Flack HD. Bernardinelli G. J. Appl. Crystallogr.  2000,  33:  1143 
  • 42 Hooft RWW. Straver LH. Spek AL. J. Appl. Crystallogr.  2008,  41:  96 
  • 43a Thompson AL. Watkin DJ. Gal ZA. Jones L. Hollinshead J. Jenkinson SF. Fleet GWJ. Nash RJ. Acta Crystallogr., Sect. C  2008,  64:  o649 
  • 43b Thompson AL. Watkin DJ. Tetrahedron: Asymmetry  2009,  20:  712 
  • 44a Smith B. Warren SC. Newton GGF. Abraham EP. Biochem. J.  1967,  103:  877 
  • 44b Baldwin JE. Coates JB. Halpern J. Moloney MG. Pratt AJ. Biochem. J.  1989,  261:  197 
  • 44c Baldwin JE. Pratt AJ. Moloney MG. Tetrahedron  1987,  43:  2565 
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 for 7b refined to -0.2 (8), however analysis of the Bijvoet pairs gave a Hooft y parameter of 0.0(3) giving a 99.2% probability that the structure is of the correct handedness (assuming full enantiopurity). 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).