RESUMEN
A general approach to 3-azabicyclo[3.1.1]heptanes by reduction of spirocyclic oxetanyl nitriles was developed. The mechanism, scope, and scalability of this transformation were studied. The core was incorporated into the structure of the antihistamine drug Rupatidine instead of the pyridine ring, which led to a dramatic improvement in physicochemical properties.
RESUMEN
A synthetic strategy to fused bicyclic piperidines-building blocks for medicinal chemistry-is developed. The key step was an intramolecular [2 + 2]-photocyclization. The photochemical step was performed on a gram scale. Crystallographic analysis of the obtained compounds revealed that they occupy a novel chemical space and can be considered as elongated analogues of 3-substituted piperidines.
Asunto(s)
Química Farmacéutica , Piperidinas , EstereoisomerismoRESUMEN
Many oxetane-carboxylic acids were found to be unstable. They easily isomerized into new (hetero)cyclic lactones while being stored at room temperature or slightly heated. Chemists should keep in mind the high instability of these molecules, as this could dramatically affect the reaction yields and lead to negative results (especially in those reactions that require heating).
Asunto(s)
Ácidos Carboxílicos , Éteres Cíclicos , Isomerismo , LactonasRESUMEN
Synthesis of the previously unknown conformationally rigid sultams fused with the cyclobutane ring was developed. The key transformation was an intramolecular photochemical cyclization of linear sulfonamides. Crystallographic analysis showed that the obtained structures populated the uncharted region in the chemical space.