Executive Summary : | Macrocyclic natural products, such as nemamides A-B, euglenatides A-E, koshidacins A-B, and enamidonins B-C, have gained attention due to their novel architectures and promising bioactivities. These members exhibit promising bioactivities, but some remain undetermined due to material scarcity. To understand their biological significance, efficient synthetic routes for chemical synthesis are needed. The proposed project aims to develop efficient synthetic routes to access targeted natural products in sufficient quantity and their variety of new analogues. Strategies for achieving unnatural β-amino acids bearing multiple chiral centers will be developed using Prins cyclisation followed by Ritter reaction sequence, while Sharpless asymmetric dihydroxylation will be tested for making unnatural amino acid 4,5-dihydroxynorvaline. The site for effective macrolactamization will be determined to obtain the required cyclic peptides, which will be stitched together with polyketide counterparts using a Heck coupling-based late-stage functionalization approach. The proposed structures of the natural products will be validated, and the unassigned stereocenter present in euglenatide C will be determined. Different chemical reactions will be tested to construct the required polypropionate parts of the targeted molecules and their different analogues. Bicyclic analogues of some targeted natural products will be prepared to explore their biological implications. All synthesized molecules will be screened for anticancer, antifungal, and antibacterial activities to find possible leads for future development. |