Research Projects

This project aims to establish a unified, asymmetric total synthesis for structurally complex norditerpene dilactones. These natural products possess a rare 6/6/6/5-fused ring skeleton and are known for their potent antifungal, anticancer, and anti-inflammatory activities. Despite the biological promise, limited synthetic accessibility and lack of scalable methodologies restrict their broader pharmacological evaluation. 1 The proposed work focuses on the development of a novel cascade reaction strategy starting from optically pure allyl alcohol derivatives. Key steps include a Pd(0)-catalyzed allylation/Diels-Alder cascade to assemble a 6/6/5-fused tricyclic scaffold, followed by methylation and oxidation steps to furnish a versatile common intermediate. This intermediate will serve as a common precursor for synthesizing a wide array of norditerpenoid natural products, including oidiolactones and nagilactones. Preliminary (Scheme 1) studies from Dr. Parthasarthi’s lab have confirmed the feasibility of this cascade strategy with high diastereoselectivity (83:17), forming the key tricyclic intermediate. The full synthetic route will be implemented in stages, comprising the synthesis of the scaffold, generation of intermediates, and final elaboration into natural products. The proposed project will enhance synthetic strategies for biologically important terpenoids. Successful outcomes will include publications and synthetic protocols for complex frameworks.