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Stereogenic and conformational properties of medium-ring benzo-fused N-heterocycle atropisomers.

Stereogenic and conformational properties of medium-ring benzo-fused N-heterocycle atropisomers.

Authors :
de Ceuninck van Capelle LA
Macdonald JM
Hyland CJT
Source :
Organic & biomolecular chemistry [Org Biomol Chem] 2021 Sep 07; Vol. 19 (33), pp. 7098-7115. Date of Electronic Publication: 2021 Jun 30.
Publication Year :
2021

Abstract

Medium-ring (7-9-membered) benzo-fused N-heterocycles - a core structure in several important pharmaceuticals - have a diverse range of interesting conformational and stereochemical properties which arise from restricted bond rotation in the non-aromatic ring. The atropisomers of these pharmaceutically relevant N-heterocycles typically exhibit different biological activities, warranting the need to deeply understand the factors controlling the conformation and stereochemistry of the systems. Beginning with a brief introduction to atropisomer classification, this review will detail a number of medium-ring benzo-fused N-heterocycle systems from the recent literature to provide an overview of structural factors which can affect the atropisomeric nature of the systems by altering the overall conformation and rate of stereo-inversion. As well as general factors such as ring-size and sterics, the impact of additional stereocentres in these systems will be addressed. This includes the differences between sulfur, nitrogen and carbon stereocentres, and the consequences of stereocentre placement around the N-heterocycle ring. Further, conformational stabilisation via non-covalent intramolecular bonds will be explored. As such, this review represents a significant resource for aiding in the design, synthesis and study of new and potentially bioactive medium-ring benzo-fused N-heterocycles.

Details

Language :
English
ISSN :
1477-0539
Volume :
19
Issue :
33
Database :
MEDLINE
Journal :
Organic & biomolecular chemistry
Publication Type :
Academic Journal
Accession number :
34190302
Full Text :
https://doi.org/10.1039/d1ob00836f