Enhanced Stereochemical Representation

Introduction

Many compounds—and in particular, those of biological interest—contain more than one stereogenic center. It can be very useful to be able to talk about the relative configuration of various stereogenic centers even in cases where the absolute configuration is not known. Enhanced stereochemistry is used to indicate that a molecule has uncertain stereochemical center, and it was supported by most of cheminformatics softwares. The enhanced stereochemical features can be used to describe a known mixture of compounds (racemic mixtures, pure enantiomers, mixture of diastereomers), instead of drawing multiple separate structures. In this piece, we aim to provide an overview of the proper use of enhanced stereochemical labels.

Enhanced Stereochemistry Labels

There are three enhanced stereochemistry labels that can be attached to a stereocenter. They are: or (OR); & (AND); and abs (ABS). AND is non-invertible label, that means the stereocenter is only present in the form drawn. OR and AND are invertible labels, that means the stereocenter either has unknown absolute configuration, or is present in both configurations.

ABS label

The ABS label is one that can be added to a chiral center to denote that it is unambiguously a pure sample of the drawn stereoisomer. This is equivalent to the “Chiral Flag” in the earlier V2000 specification of the molfile, albeit at the level of the particular chiral center, and not generalized to the entire molecule. The necessity of using this label may be a point of contention; while the official MDL specification states that any chiral center not featuring an ABS label is not pure/some form of unknown, many practicing chemists (as well as the IUPAC recommendations) state that one should assume a pure stereoisomer when no further information is added. For the purposes of this document, we will consistently add the ABS label for the sake of completeness, however most cheminformatics applications have a default configuration setting of “assume absolute stereochemistry”.

OR label

The OR label is used to describe stereogenic center where the relative configuration is known, but the absolute configuration is not known. The structure represents one stereoisomer that is either the structure as drawn (R,S) or the epimer in which the stereogenic centers have the opposite configuration (S,R). The two possible variations at the OR label means that only one of the two structure is present-but we don't know which.

The structure above, indicates one of the 8 structures below

AND label

The AND label indicates a mixture of stereoisomers, both the drawn configuration and its inverse are present. It can be a pair of enantiomers or all the diastereomers. When the AND stereogroup contains just one center, AND indicates that both the drawn configuration and its epimer are present.

The structure above, indicates a mixture of below 4 structures

If the number of two stereocenters is the same, the centers must change together. AND numbering is always independent of OR numbering.

Examples

Example 1

The structure above, indicates one of below two structures:

Example 2

The structure above, indicates one of the two mixture.

Example 3

The structure above, indicates either a mixture of below 4 structures:

Or a mixture of below 4 structures:

The two possible variations at the OR label means that only one of the two structure is present-but we don't know which. Two independent AND centers means that, with the confine of OR label, all 4 structures are present as a mixture. Again, note AND and OR numbering is independent, AND 1 don't effect OR 1.

Pseudo Chirality

Pseudo stereocenters are very different when applying enhanced stereochemistry labels. For bellow structures, the different labels indicates the same molecule.

Conclusion

This post gives an introduction to the enhanced stereochemistry representation, and describe the three enhanced stereo labels: ABS, AND, and OR. Applying the enhanced stereo labels, we can describe mixture of enantiomers or diastereomers, and uncertain pure enantiomer conveniently without drawing multiple separate structures.