P9 Design and synthesis of novel archazolids: development of simplified analogues

The polyketide natural products archazolid A and B constitute novel types of particularly efficient and specific inhibitors of V ATPases, which have been shown to demonstrate potent antitumor activity in mice, which renders them highly attractive compounds for further preclinical advancement. However this has been hampered by the low availability from their natural source and the structural complexity that impedes a large scale access by total synthesis.

This project proposes the design and synthesis of simplified archazolids as improved antitumor agents. Particular emphasis will be placed on the development of equipotent but more readily available analogues. Structural simplification will rely on a rational approach based on a detailed in silico analysis of target inhibitor interactions. These compounds will be obtained either by a modular, total synthesis or based on derivatization of the parent natural products themselves. 

Principal investigator: 

DFG-funded scientists: 

  • Stephan Scheef, PhD student