Total Synthesis of Aleutianamine

• Applicant: Dr. Fabian Martin Hörmann
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 455799816

Pancreatic cancer is one of the deadliest type of cancer, since existing therapy options have only little chance for a cure. The alkaloid Aleutianamine was isolated in 2019 from the sponge Latrunculia austini Samaii and exhibits a remarkable activity against pancreatic cancer cell lines (PANC-1) in the nanomolar range. Besides the intriguing biological activity, Aleutianamine displays a multibridged and highly strained ring system containing three stereogenic centers making it the structurally most complex member of the natural product class of pyrroloiminoquinones. The objective of this proposal is the first total synthesis of Aleutianamine using one of the two proposed strategies. The first approach aims for a minimum number of steps and features a novel diastereoselective 1,3-dipolar cycloaddition as the key step. The development of this methodology would enable access to complex and novel structural frameworks related to Aleutianamine. A high chance of success can be attributed to the second approach, which is longer but some of the critical transformations have been validated in total syntheses of the closely related Discorhabdins. Furthermore, both strategies are suitable for the synthesis of natural product derivatives and thus will enable preliminary studies regarding the structure-activity relationships.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Christopher Vanderwal, Ph.D.