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Metal‐Free meta ‐Selective Alkyne Oxyarylation with Pyridine N ‐Oxides: Rapid Assembly of Metyrapone Analogues
Author(s) -
Chen Xiangyu,
Ruider Stefan A.,
Hartmann Rolf W.,
González Leticia,
Maulide Nuno
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201607988
Subject(s) - pyridine , chemistry , alkyne , combinatorial chemistry , density functional theory , metyrapone , medicinal chemistry , stereochemistry , computational chemistry , organic chemistry , catalysis , medicine
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.