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Total Synthesis of Waixenicin A and Xenibellol A

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSITAET INNSBRUCK
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 174 167,04
Address
INNRAIN 52
6020 Innsbruck
Austria

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Region
Westösterreich Tirol Innsbruck
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 174 167,04
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