Synlett 2016; 27(14): 2039-2042
DOI: 10.1055/s-0035-1561638
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© Georg Thieme Verlag Stuttgart · New York

Bioinspired Discovery of Chemical Reactions and Biological Probes

Brendan M. Griffiths
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA   Email: xiang.wang@colorado.edu
,
Jessica D. Burl
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA   Email: xiang.wang@colorado.edu
,
Xiang Wang*
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA   Email: xiang.wang@colorado.edu
› Author Affiliations
Further Information

Publication History

Received: 23 March 2016

Accepted after revision: 13 April 2016

Publication Date:
06 June 2016 (online)

This paper is dedicated to Professor Stuart L. Schreiber on the occasion of his 60th birthday.

Abstract

Indole alkaloids are a large and diverse family of natural products that display a variety of medicinal properties. These natural products have consistently proven difficult to synthesize, due in large part to their complex skeletons and sterically hindered quaternary carbon centers. We have reported the efficient syntheses of polycyclic indole derivatives using gold catalysts, which selectively activate alkynylindoles for tandem cyclizations with high stereospecificity. The facile nature of these methods has allowed previously implausible diversity syntheses to be carried out yielding a large and highly diverse library of polycyclic indolines. Biological screenings revealed compounds that selectively re-sensitize methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics, which may herald a new way of staving off the incursion of drug-resistant strains of common human pathogens.

1 Introduction

2 Gold-Catalyzed Cyclizations

3 Chemical Probe Discovery

4 Outlook

 
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