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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;
Further Information

Publication History

Received 15 November 2010
Publication Date:
19 January 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

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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).