RESUMEN
The need for reliable information storage is on a steep rise. Sequence-defined polymers, particularly oligonucleotides, are already in use in several areas, while compound mixtures also offer a simple way for storing information. We investigated the use of a set of isotopologues in information storage by mixing, where the information is stored in the form of a mass spectrometric (MS) fingerprint of the mixture. A small molecule with 24 non-labile and replaceable hydrogen atoms was selected as a model, and a set of components covering the D0-D24 deuteration range were synthesized. Theoretical analysis predicted that by mixing up to 10 out of the prepared components, one can encode over 130 million different combinations and distinguish their MS fingerprints. As a proof of principle, several mixtures predicted to have similar fingerprints were prepared and their MS fingerprints were recorded. From each measured MS fingerprint, we were able to unambiguously identify the actual composition of the mixture. It was also demonstrated that one can make the MS fingerprints of a given mixture unique, thereby making counterfeiting of the stored information very difficult. Finally, the utility of isotope ratio encoding in covalent tagging was also demonstrated.
RESUMEN
Amide bioisoterism is a widely used strategy in drug development to fine-tune physicochemical, pharmacokinetic, and metabolic properties, eliminate toxicity and gain intellectual property rights in uncharted chemical space. Of these, oxetane-amines offer particularly exciting possibilities as bioisosteres, although they are less frequently investigated than warranted due to the lack of simple and widely applicable synthetic methods. Herein, we report a two-step, practical, modular, robust, and scalable method for the construction of oxetane-containing amide bioisosteres that relies on the readily available oxetan-3-one. This operationally simple procedure exploits the enhanced reactivity of the keto group of the commercially available oxetan-3-one to form amine-benzotriazole intermediates, which springloaded adducts are then reacted with various aliphatic and aromatic organometallic reagents under mild conditions to afford various amino-oxetanes in good to high yields. The simplicity and broad applicability of the method greatly facilitates the synthesis of derivatives that were previously difficult or impossible to produce. The usefulness of this method in the field medicinal chemistry was also demonstrated by eliminating the well-known metabolic problem of ketoconazole.