Atropisomer

[1] The word atropisomer (Greek: ἄτροπος, atropos, meaning "not to be turned") was coined in application to a theoretical concept by German biochemist Richard Kuhn for Karl Freudenberg's seminal Stereochemie volume in 1933.

[4] Atropisomerism was first experimentally detected in a tetra substituted biphenyl, a diacid, by George Christie and James Kenner in 1922.

[10] Determining the axial stereochemistry of biaryl atropisomers can be accomplished through the use of a Newman projection along the axis of hindered rotation.

The most important class of atropisomers are biaryls such as diphenic acid, which is a derivative of biphenyl with a complete set of ortho substituents.

Heteroaromatic analogues of the biphenyl compounds also exist, where hindered rotation occurs about a carbon-nitrogen or a nitrogen-nitrogen bond.

In a similar way, aliphatic ring systems like cyclohexanes linked through a single bond may display atropisomerism provided that bulky substituents are present.

Their ability to provide stereoinduction has led to use in metal catalyzed hydrogenation, epoxidation, addition, and allylic alkylation reactions.

[18] A recent example in the area of chiral biaryl asymmetric catalysis employs a five-membered imidazole as part of the atropisomer scaffold.

[1][21] Other examples of naturally occurring atropisomers include vancomycin isolated from an Actinobacterium, and knipholone, which is found in the roots of Kniphofia foliosa of the family Asphodelaceae.

Knipholone, with its axial chirality, occurs in nature and has been shown to offer good antimalarial and antitumor activities particularly in the M form.

Atropisomers also might interact differently in the body, and as with other types of stereoisomers, it is important to examine these properties before administering drugs to patients.