Metal‐Free meta‐Selective Alkyne Oxyarylation with Pyridine N‐Oxides: Rapid Assembly of Metyrapone Analogues. Issue 49 (9th November 2016)

• Record Type: Journal Article
• Authors: Chen, Xiangyu; Ruider, Stefan A.; Hartmann, Rolf W.; González, Leticia; Maulide, Nuno
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 49(2016)
• Page Start: 15424
• Page End: 15428
• Publication Date: 2016-11-09
• Subjects: 11β-hydroxylase (CYP11B1) -- alkynes -- density functional calculations -- oxyarylations -- pyridine N-oxides; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201607988
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : New leads : The title reaction affords meta ‐substituted pyridines analogous to the drug metyrapone with high regioselectivities. DFT calculations revealed an elaborate rearrangement cascade involving unusual [3, 5] pseudopericyclic reactions. Biological studies indicate that some of these products are active CYP11B1 inhibitors.