Grant: Discovery Grants Program - Individual

The property of chirality or "handedness" pervades the world in which we live. The phenomenon of molecular chirality, which refers to molecules that are identical in their connectivity but differ in their spatial arrangements, was first recognized by the Nobel Prize winner van't Hoff in 1874. Since then the phenomenon of molecular chirality has become of significant importance with the realization that molecules can have dramatically different physiological effects depending on their chirality. As such the ability to selectively prepare chiral molecules is therefore currently of pressing importance to chemists. The field of asymmetric catalysis ("Chiral Synthesis using Catalysts") is making this goal achievable through the use of small quantities of additives known as catalysts which selectively afford either "handed" isomer of a desired chiral compound. It is in this vein that the proposed research outlines an innovative approach which combines experimental practice with first principles computational insight. As such, proposed is an in silico assisted invention of efficient "one-pot" asymmetric Sequential Tandem Catalysis (STC) and Concurrent Tandem Catalysis (CTC) protocols which allow in practice, and foreseeably will continue to allow, access to a diverse array of optically enriched biologically active heterocycles. Regarding the latter, the proposed STC- and CTC-methodologies are serving as key synthetic transformations within a total synthesis of (+)-spirolaxine methyl ether which is a metabolite of fungus Sporotrichum laxum that possesses inhibitory activity against Helicobacter pylori. To briefly comment the inhibitory activity of (+)-spirolaxine methyl ether is significant in that the presence of H. pylori, which lives beneath the mucus layer of the stomach, is intimately correlated with the development of gastric and duodenal ulcers. It goes without saying that the proposed research will not only contribute to the field of organic synthesis, but as well will have a positive impact on humankind's quality of life.