Modular Synthesis of Diverse Natural Product-like Macrocycles: Discovery of Hits with Antimycobacterial Activity

A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12-20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity

Divergent Approach to Building a Latrunculin Family Derived Hybrid Macrocyclic Toolbox

A divergent approach to obtain a latrunculin family based hybrid macrocyclic toolbox is developed. A practical, stereoselective synthesis of a common substructure present in latrunculin A and latrunculol A was achieved. This was further utilized in the macrocyclic diversity synthesis. The amino acid moiety embedded in the 15-membered macrocyclic ring allows for the exploration of various chiral side chains as one of the diversity sites