Recent Advances in Stereochemistry Reveal Classification Shortcomings

We contend that the Polytope model utilized by IUPAC to specify stereoisomerism for species ML_n with n > 3 should be universally applied. Such application recently led to the synthesis of isolable compounds displaying a new fundamental form of isomerism, akamptisomerism, pertinent to ML₂ stereocenters. We review 443807 molecules that could be classified as akamptisomers. Some akamptisomers are described as being “wrong” by existing IUPAC rules, hindering molecular conception. For many classes of medicinal and technology-related molecules, software packages like ChemDraw mostly do not handle akamptisomers correctly, databases such as CAS provide 2D representations inconsistent with those presented in the original publications, and often the akamptisomeric identity of compounds remains unknown. These features hinder both human and machine-learning approaches to chemical design. Further, the existence of previously unrecognized isomeric forms has broad implications for patents and pharmaceutical-registration requirements. Hence, the immediate re-examination of stereochemistry is demanded.