Abstract:
Despite the ever-expanding toolbox of reactions available to synthetic chemists, the efficient and scalable synthesis of stereochemically complex molecules remains a significant challenge and a bottleneck in the drug discovery process. Here, our efforts to address these challenges in two distinct areas (nucleoside analogues and diterpenoid natural products) will be discussed. In Part I, our efforts to develop a robust and scalable de novo synthesis of nucleosides will be presented along with its application in the synthesis of high-value nucleoside analogues and recent extension to nucleoside library production. In Part II, a recently completed total synthesis of the antimitotic natural products sarcodictyin A and eleutherobin will be showcased along with the generation of unnatural analogues of these potentially important anticancer agents.