Project description
Novel synthetic route provides access to corals' potentially life-saving compounds
Waixenicin A and xenibellol A, natural products extracted from (marine) soft corals, exhibit cytotoxic and antibacterial activity and are gaining increasing interest for their application as anticancer agents. The ability to produce them synthetically could open the door to the development and testing of novel drugs to treat cancer, yet it has so far been elusive. The EU-funded SynWaiXen project is planning to break this barrier using a newly reported organocatalytic method that not only promises access to these novel anticancer agents but, due to the speed and efficiency of the reaction, should also accomplish it quickly and sustainably. Success could get drugs based on these novel marine agents into the pharmaceutical development pipeline and, hopefully, out to the patients who need them.
Objective
The realization of the first total syntheses of the two marine natural products waixenicin A and xenibellol A is the aim of this proposal. For this purpose, a N-heterocyclic carben (NHC)-catalyzed bicyclization shall be employed as key transformation. Both target structures are members of the Xenia diterpenoids family and exhibit cytotoxicity against human cancer cell lines. Despite these highly desirable, promising biological properties and unique structural features, therapeutic applications have been prevented by the circumstance that no synthetic access has been achieved until this day. Using retrosynthetic pattern recognition, we realized that the central fused lactone motif (of both natural products) could be efficiently accessed via a recently reported NHC-catalyzed bicyclization reaction. This organocatalytic methodology enables a rapid creation of molecular complexity and, therefore, its application to these total syntheses should save time and other resources. If a therapeutic potential can be corroborated, a synthetic access would provide this family of Xenia diterpenoids (or their derivatives) as possible anticancer drugs. As a result, this project could potentially lead to an improvement of medical care for future cancer patients, thereby also addressing a UN sustainable development goal.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
6020 Innsbruck
Austria