Metal‐Free meta‐Selective Alkyne Oxyarylation with Pyridine N‐Oxides: Rapid Assembly of Metyrapone Analogues

Chen, Xiangyu; Ruider, Stefan A.; Hartmann, Rolf W.; González, Leticia; Maulide, Nuno

doi:10.1002/anie.201607988

Angewandte Chemie International Edition

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Metal-Free meta-Selective Alkyne Oxyarylation with Pyridine N-Oxides: Rapid Assembly of Metyrapone Analogues

Authors

Dr. Xiangyu Chen,
1. Institute of Organic Chemistry, University of Vienna, Vienna, Austria
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Dr. Stefan A. Ruider,
1. Institute of Organic Chemistry, University of Vienna, Vienna, Austria
2. Institute of Theoretical Chemistry, University of Vienna, Vienna, Austria
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Prof. Dr. Rolf W. Hartmann,
1. Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research, Saarbrücken, Germany
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Prof. Dr. Leticia González,
1. Institute of Theoretical Chemistry, University of Vienna, Vienna, Austria
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Prof. Dr. Nuno Maulide
Corresponding author
- E-mail address: nuno.maulide@univie.ac.at
1. Institute of Organic Chemistry, University of Vienna, Vienna, Austria
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First published: 9 November 2016Full publication history
DOI: 10.1002/anie.201607988 View/save citation
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Abstract

An efficient metal-free oxyarylation of electron-poor alkynes with pyridine N-oxides has been developed. This transformation affords meta-substituted pyridines analogous to the drug metyrapone in high regioselectivities. Density functional theory (DFT) calculations provided important insight into the mechanism. Evaluation of the inhibitory properties revealed the most active CYP11B1 inhibitor of these derivatives, with two-digit nanomolar inhibitory activity akin to that of metyrapone.

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DOI

10.1002/anie.201607988

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Keywords

11β-hydroxylase (CYP11B1);
alkynes;
density functional calculations;
oxyarylations;
pyridine N-oxides

Publication History

Issue online: 29 November 2016
Version of record online: 9 November 2016
Manuscript Revised: 13 September 2016
Manuscript Received: 16 August 2016

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