Advances in the synthesis of drugs "through Alice’s looking glass"

“Would you like to live in the mirror house, kitty? I wonder if they would give you milk there; but perhaps the milk in the mirror is not good to drink”. Lewis Carroll already imagined in 1871 that objects contained in the reflection of a mirror could well not have the same properties as “real” objects. The fact of observing two images of the same object, one of them a reflection of the other, led Alice to consider this conjecture in the book “Through the Looking Glass and what Alice found there”, and they were renowned scientists, such as Pasteur, who had the opportunity to demonstrate it in their laboratories through the study of the molecules that make up matter: the images of the molecular structures of tartaric acid (present in many fruits, especially grapes) on the two sides of the mirror resulted be non-superimposable (that is, they cannot be superimposed, as happens with the two hands of a person) and also presented different properties. These molecular structures are known as enantiomers of tartaric acid.

Today it is known that in therapeutic targets, where a drug exerts its action, it is necessary to have only one of the two mirror images (the molecular structure of one of the sides of the mirror) or enantiomers of a drug to achieve the effect. wanted. Likewise, possible side effects that may be caused by the opposite enantiomer, milk in the reflection of Lewis Carroll’s story, are reduced and even eliminated. A research group from the Faculty of Science and Technology, the Asymmetric Synthesis, Sustainable Chemistry and Biomimetic Processes Group led by Professor José Luis Vicario of the University of the Basque Country (UPV/EHU), has been working on the field for more than two decades. discovery of new methodologies aimed at the preferential preparation of a single enantiomer for the synthesis of different drugs and natural products of therapeutic interest.

Recently, and in collaboration with Professor Merino from the University of Zaragoza, in Spain, they have developed a novel way for the creation of polycyclic compounds, managing to generate a single enantiomer of the two possible ones, thanks to an operation on a molecular scale through catalysis.

Uxue Uria Pujana and Jose Luis Vicario. (Photo: Red Jabi)

The methodology used in this research, as well as the usefulness of the compounds obtained, have been recognized by the academic journal Chemistry: A European Journal, where the study has been published. Vicario, Javier Luis-Barrera (UPV/EHU), Uxue Uria Pujana (UPV/EHU) and their colleagues have been invited to design the cover of the issue in which their study appears. On the cover, Alice is shown crossing the mirror about to become her enantiomeric form (in her mirror image) and encountering a catalyst that accompanies her on the yellow path until forming the final product, a sulfonamide.

The study is titled “Brønsted Acid versus Phase-Transfer Catalysis in the Enantioselective Transannular Aminohalogenation of Enesultams”. (Source: UPV/EHU)