Triterpenoid bis-amide analogs via Ugi reaction

Isocyanide-based Multicomponent Reactions (IMCRs) are domino processes in which three or more components react to form a complex molecule containing all or most of the atoms of starting materials. They have several advantages over multistep syntheses and other domino processes, e.g. convergence, modularity, operational simplicity, safety, high overall yields and lower costs. IMCRs are recognized as one of the best synthetic tools in organic chemistry; furthermore, they fulfill most of Green Chemistry Principles and are considered as the closest to an ideal synthesis in the green chemistry field.

Ugi four-component reaction (Ugi-4CR) is the most studied IMCR, and typically involves an isocyanide, a carbonyl compound, an amine and a carboxylic acid. It has proven to be an efficient and rapid tool for the synthesis of bis-amides, a peptidomimetic scaffold which is relevant for medicinal chemistry and organic synthesis. In the latter, they can be used as synthetic platform for synthesizing heterocycles, bis-heterocycles and even polyheterocycles via IMCR-post transformation strategies.

Recently, Ugi-4CR has been successfully applied for the synthesis of triterpenoid analogs, however this field is still underexplored, and several downsides can be observed, such as long reaction times and moderate yields.

Herein, we present the synthesis of a small series of bis-amide triterpenoid analogs employing masticadienonic acid, a triterpenoid with carboxylic acid function isolated from aerial parts of Pistacia mexicana.