Synthetic study toward angucycline and resin glycoside natural products

• Online Access: http://hdl.handle.net/2047/d20003218

Angucycline natural products containing carbohydrate motifs have long been known for their impressive biological activities. Apart from their interesting bioactivities, these complex natural products are challenging synthetic targets. A practical total synthetic approach toward these natural products enables adequate material for Structure Activity Relationship (SAR) studies, which are rather limited from the natural sources. These multi-step syntheses also help uncover the information about the structure reactivity and discovery of important/new organic transformations. The carbohydrate portion of natural products plays a crucial role in the bioactivities they exhibit in parts by improving the pharmacokinetic and physiochemical properties (target binding, solubility, tissue targeting, and membrane transportation). The O'Doherty group has developed a de novo asymmetric approach to build the desired functionality and stereochemistry within each sugar starting from an achiral starting material, in contrast to the traditional approaches using known carbohydrates as starting materials. The de novo approach relies on a highly diastereoselective palladium(0)-catalyzed glycosylation reaction to control the anomeric stereocenter and post-glycosylation transformation to introduce the corresponding functionality and stereocenters in the sugar moiety. Continuing our group's long lasting interest in carbohydrate chemistry and the utility of this strategy, attention was turned to the syntheses of the bioactive carbohydrate-based angucycline natural product analogues.