Total synthesis of antimicrobial and antitumor cyclic depsipeptides

The total synthesis of natural products "has to be viewed as an art and a science that needs to be advanced for its own sake" (K. C. Nicolaou) and indeed, the achievements within this field of chemistry during the last decades are astonishing. However, besides its inherent beauty, total synthesis also opens the gates widely to a better understanding of biological processes and the development of pharmaceutical interesting substances. Cyclic depsipeptides form one of the compound classes that have attracted tremendous attention from synthetic chemists. They often feature non-proteinogenic amino acids and various types of structural unique building blocks, which make them challenging targets for synthetic efforts. Their total synthesis offers the chance to implement the use of newly developed synthetic tools in a complex environment. Synthetic dead-ends have shown the limitations of today's chemistry as well as triggering the development of new methodologies to circumvent the observed problems. Cyclic depsipeptides also often possess biological properties, especially antimicrobial and antitumor activity, that make them promising candidates for further pharmaceutical investigations and thus have a value at their own. Furthermore, through construction from scratch, ambiguities regarding the structure of several members of that compound class could be successfully clarified and derivatives for structure-activity-relationship (SAR) studies obtained.