Executive Summary : | Inflammation is a complex biological response of the immune system to infections, injuries, or other harmful stimuli. Anti-inflammatory drugs work by inhibiting various inflammatory pathways or targeting transcription factors, or by inhibiting the production of mediators of inflammation. However, these drugs have drawbacks such as poor pharmacokinetic profile and toxicity, which can mask their efficacy. Prolonged use can have severe toxic effects on organ systems like the gastrointestinal, cardiovascular, renal, liver, and lungs. There is a pressing need for new anti-inflammatory agents, and naturally abundant and economically affordable chiral terpenes serve as useful building blocks for synthesis of complex natural products. Advances in synthetic methodologies have allowed for rapid excess to structural complex molecules with varied skeleta and abundant stereochemistry. Labdane diterpene sclareol, a polycyclic terpene, often serves as a starting point for the synthesis of various natural products. Heterocycles are the structural components of many biologically important natural products, and their structural motifs are embedded in other natural products to enhance their bioactivities. To explore the structural, functional, and stereochemical framework of sclareol, libraries of pyrano-oxepines, amido pyrano-oxepines, and pyrano-piperidines will be synthesized using Prins-type cyclization reactions. The heterocycle-based marine natural product Echinolabdane A will be synthesized using scalreol as a template. All newly synthesized candidates will be evaluated for their anti-inflammatory potential. |