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

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.

heterocycles - natural products - cyclisation - antibiotics - lactams

References and Notes

<A NAME="RD30410ST-1A">1a</A> Kotra LP. Golemi D. Vakulenko S. Mobashery S. Chem. Ind. (London)  2000,  341 

<A NAME="RD30410ST-1B">1b</A> Niccolai D. Tarsi L. Thomas RJ. Chem. Commun.  1997,  2333 

<A NAME="RD30410ST-1C">1c</A> Peet NP. Drug Discovery Today  2010,  15:  583 

<A NAME="RD30410ST-2A">2a</A> Morel C. Mossialos E. Br. Med. J.  2010,  340:  1115 

<A NAME="RD30410ST-2B">2b</A> So AD. Gupta N. Cars O. Br. Med. J.  2010,  340:  1091 

<A NAME="RD30410ST-3">3</A> Newman DJ. Cragg GM. J. Nat. Prod.  2007,  70:  461 

<A NAME="RD30410ST-4A">4a</A> Danishefsky S. Nat. Prod. Rep.  2010,  27:  1114 

<A NAME="RD30410ST-4B">4b</A> 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 

<A NAME="RD30410ST-4C">4c</A> Galloway WRJD. Bender A. Welch M. Spring DR. Chem. Commun.  2009,  2446 

<A NAME="RD30410ST-4D">4d</A> Cordier C. Morton D. Murrison S. Nelson A. O’Leary-Steele C. Nat. Prod. Rep.  2008,  25:  719 

<A NAME="RD30410ST-4E">4e</A> Newman DJ. J. Med. Chem.  2008,  51:  2589 

<A NAME="RD30410ST-5A">5a</A> vonNussbaum F. Brands M. Hinzen B. Weigand S. Habich D. Angew. Chem. Int. Ed.  2006,  45:  5072 

<A NAME="RD30410ST-5B">5b</A> 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 

<A NAME="RD30410ST-5C">5c</A> Baltz RH. J. Ind. Microbiol. Biotechnol.  2006,  33:  507 

<A NAME="RD30410ST-5D">5d</A> Gullo VP. McAlpine J. Lam KS. Baker D. Petersen F. J. Ind. Microbiol. Biotechnol.  2006,  33:  523 

<A NAME="RD30410ST-5E">5e</A> Koch MA. Waldmann H. Drug. Discovery Today  2005,  10:  471 

<A NAME="RD30410ST-5F">5f</A> Koehn FE. Carter GT. Nat. Rev. Drug Discovery  2005,  4:  206 

<A NAME="RD30410ST-5G">5g</A> Shang S. Tan DS. Curr. Opin. Chem. Biol.  2005,  9:  248 

<A NAME="RD30410ST-5H">5h</A> Ganesan A. Curr. Opin. Biotechnol.  2004,  15:  584 

<A NAME="RD30410ST-5I">5i</A> Njardarson JT. Gaul C. Shan D. Huang X.-Y. Danishefsky SJ. J. Am. Chem. Soc.  2004,  126:  1038 

<A NAME="RD30410ST-5J">5j</A> Rouhi AM. Chem. Eng. News  2003,  81:  77 

<A NAME="RD30410ST-5K">5k</A> Breinbauer RB. Vetter IR. Waldmann H. Angew. Chem. Int. Ed.  2002,  41:  2878 

<A NAME="RD30410ST-5L">5l</A> Hemkens PHH. Ottenheijm HCJ. Rees DC. Tetrahedron  1997,  53:  5643 

<A NAME="RD30410ST-6">6</A> O’Shea R. Moser HE. J. Med. Chem.  2008,  51:  2871 

<A NAME="RD30410ST-7A">7a</A> Hajduk PJ. J. Med. Chem.  2006,  49:  6972 

<A NAME="RD30410ST-7B">7b</A> Rees DC. Congreve M. Murray CW. Carr R. Nat. Rev. Drug Discovery  2004,  3:  660 

<A NAME="RD30410ST-8A">8a</A> Balamurugan R. Dekkerab FJ. Waldmann H. Mol. BioSyst.  2005,  1:  36 

<A NAME="RD30410ST-8B">8b</A> 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 

<A NAME="RD30410ST-9">9</A> Zhou J. Xie G. Yan X. Traditional Chinese Medicines   Ashgate; England: 2004. 

<A NAME="RD30410ST-10">10</A> Anwar M. Cowley AR. Moloney MG. Tetrahedron: Asymmetry  2010,  21:  1758 

<A NAME="RD30410ST-11">11</A> Jeong Y.-C. Moloney MG. Synlett  2009,  2487 

<A NAME="RD30410ST-12A">12a</A> Chandan N. Moloney MG. Org. Biomol. Chem.  2008,  6:  3664 

<A NAME="RD30410ST-12B">12b</A> Hill T. Kocis P. Moloney MG. Tetrahedron Lett.  2006,  47:  1461 

<A NAME="RD30410ST-13">13</A> 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 

<A NAME="RD30410ST-14">14</A>

Communication from Shanghai Innovative Research Center of Traditional Chinese Medicine.

<A NAME="RD30410ST-15">15</A> Karadeolian A. Kerr MA. Angew. Chem. Int. Ed.  2010,  49:  1133 

<A NAME="RD30410ST-16">16</A> Andrews MD. Brewster AG. Moloney MG. Synlett  1996,  612 

<A NAME="RD30410ST-17">17</A> Andrews MD. Brewster AG. Crapnell KM. Ibbett AJ. Jones T. Moloney MG. Prout K. Watkin D. J. Chem. Soc., Perkin Trans. 1  1998,  223 

<A NAME="RD30410ST-18">18</A>

The diffraction data for 7b and 15a were collected at 150 K^³7 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 parameter^4² 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.

<A NAME="RD30410ST-19">19</A> Galeotti N. Poncet J. Chiche L. Jouin P. J. Org. Chem.  1993,  58:  5370 

<A NAME="RD30410ST-20">20</A> Andrews MD. Brewster AG. Moloney MG. J. Chem. Soc., Perkin Trans. 1  2002,  80 

<A NAME="RD30410ST-21">21</A> Ling T. Macherla VR. Manam RR. McArthur KA. Potts BCM. Org. Lett.  2007,  9:  2289 

<A NAME="RD30410ST-22">22</A> Cottrell IF. Cowley AR. Croft LJ. Hymns L. Moloney MG. Nettleton EJ. Smithies HK. Thompson AL. Tetrahedron  2009,  65:  2537 

<A NAME="RD30410ST-23">23</A> Cottrell IF. Moloney MG. Smithies HK. Tetrahedron Lett.  2009,  50:  1097 

<A NAME="RD30410ST-24">24</A> Moloney MG. Nettleton E. Smithies K. Tetrahedron Lett.  2002,  43:  907 

<A NAME="RD30410ST-25A">25a</A> Moloney MG. Main Group Met. Chem.  2001,  24:  653 

<A NAME="RD30410ST-25B">25b</A> Buston JEH. Claridge TDW. Moloney MG.
J. Chem. Soc., Perkin Trans. 2  1995,  639 

<A NAME="RD30410ST-26">26</A> Corey EJ. Reichard GA. J. Am. Chem. Soc.  1992,  114:  10677 

<A NAME="RD30410ST-27">27</A>

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).

<A NAME="RD30410ST-28">28</A>

Marvin was used for drawing, displaying and structure property prediction and calculation (ClogD_7.4, PSA, MSA and CMR calculations), Marvin 5.2.1, 2009, ChemAxon (http://www.chemaxon.com).

<A NAME="RD30410ST-29">29</A> Ferrara P. Apostolakis J. Caflisch A. Proteins: Struct., Funct., Bioinf.  2002,  46:  24 

<A NAME="RD30410ST-30A">30a</A> Padrón JA. Carrasco R. Pellón RF. J. Pharm. Pharmaceut. Sci.  2002,  5:  258 

<A NAME="RD30410ST-30B">30b</A> Ghose AK. Crippen GM. J. Chem. Inf. Comput. Sci.  1987,  27:  21 

<A NAME="RD30410ST-30C">30c</A> Viswanadhan VN. Ghose AK. Reyankar GR. Robins RK. J. Chem. Inf. Comput. Sci.  1989,  29:  163 

<A NAME="RD30410ST-31">31</A> Ertl P. Rohde B. Selzer P. J. Med. Chem.  2000,  43:  3714 

<A NAME="RD30410ST-32">32</A> Ertl P. ‘Polar Surface Area’, in Molecular Drug Properties   Mannhold R. Wiley-VCH; Weinheim: 2007.  p.111-126  

<A NAME="RD30410ST-33">33</A> Reymond J.-L. van Deursen R. Blum LC. Ruddigkeit L. MedChemComm  2010,  1:  30 

<A NAME="RD30410ST-34">34</A> Hajduk PJ. Greer J. Nat. Rev. Drug Discovery  2007,  211 

<A NAME="RD30410ST-35">35</A> Anwar M. Moloney MG. Tetrahedron Lett.  2007,  48:  7259 

<A NAME="RD30410ST-36A">36a</A> Bagwell CL. Moloney MG. Thompson AL. Bioorg. Med. Chem. Lett.  2008,  18:  4081 

<A NAME="RD30410ST-36B">36b</A> Bagwell CL. Moloney MG. Yaqoob M. Bioorg. Med. Chem. Lett.  2010,  20:  2090 

<A NAME="RD30410ST-37">37</A> Cosier J. Glazer AM. J. Appl. Crystallogr.  1986,  19:  105 

<A NAME="RD30410ST-38">38</A> Otwinowski Z. Minor W. Methods Enzymol.  1997,  276:  307 

<A NAME="RD30410ST-39">39</A> Altomare A. Cascarano G. Giacovazzo G. Guagliardi A. Burla MC. Polidori G. Camalli M. J. Appl. Crystallogr.  1994,  27:  435 

<A NAME="RD30410ST-40">40</A> Betteridge PW. Carruthers JR. Cooper RI. Prout K. Watkin DJ. J. Appl. Crystallogr.  2003,  36:  1487 

<A NAME="RD30410ST-41A">41a</A> Flack HD. Acta Crystallogr., Sect. A  1983,  39:  876 

<A NAME="RD30410ST-41B">41b</A> Flack HD. Bernardinelli G. J. Appl. Crystallogr.  2000,  33:  1143 

<A NAME="RD30410ST-42">42</A> Hooft RWW. Straver LH. Spek AL. J. Appl. Crystallogr.  2008,  41:  96 

<A NAME="RD30410ST-43A">43a</A> Thompson AL. Watkin DJ. Gal ZA. Jones L. Hollinshead J. Jenkinson SF. Fleet GWJ. Nash RJ. Acta Crystallogr., Sect. C  2008,  64:  o649 

<A NAME="RD30410ST-43B">43b</A> Thompson AL. Watkin DJ. Tetrahedron: Asymmetry  2009,  20:  712 

<A NAME="RD30410ST-44A">44a</A> Smith B. Warren SC. Newton GGF. Abraham EP. Biochem. J.  1967,  103:  877 

<A NAME="RD30410ST-44B">44b</A> Baldwin JE. Coates JB. Halpern J. Moloney MG. Pratt AJ. Biochem. J.  1989,  261:  197 

<A NAME="RD30410ST-44C">44c</A> Baldwin JE. Pratt AJ. Moloney MG. Tetrahedron  1987,  43:  2565