Total Synthesis of the Marine Diterpenoid Elisabethin A

Elisabethin A is a marine natural product that was first isolated in 1998 from the extract of a gorgonian coral together with other relatives. The members of the natural product class of these so-called "elisabethanes" exhibit rare carbon skeletons and were shown to possess numerous biological activities such as anti- inflammatory, antibacterial as well as cytotoxic effects. However, the pharmacological properties of elisabethin A itself have not yet been investigated. Their elucidation could contribute to the development of new drugs in the light of the principally promising bioactivities of this class of natural products. For this purpose, the development of a route for the synthetic production of elisabethin A would be extremely helpful, since the isolation of natural material is very elaborate and, moreover, cannot provide the required quantities. Several attempts have been made in the past to establish a synthetic route for the total synthesis of elisabethin A, all of which have so far been unsuccessful. Therefore, the aim of this project is to apply a novel, variable synthesis strategy for the artificial production of the target molecule in order to elucidate its biological activities and to investigate the relationship between different structural elements and their pharmacological modes of action.

Elisabethin A is a marine natural product that was first isolated from a coral in 1998 and belongs to a special group of chemical compounds known for their unusual structure. Some related substances in this group have shown anti-inflammatory, antibacterial and cell-damaging properties. However, it is not yet clear whether elisabethin A has similar effects, as the substance could not be comprehensively investigated due to the small amount available and the fact that it has not yet been produced artificially in the laboratory. The goal of the project was to develop a way to produce elisabethin A synthetically for the first time - a major scientific challenge. Previous attempts to synthesize this molecule failed, mainly due to the exceptionally complex structure of elisabethin A. Our approach was to build up the complex structure of the molecule efficiently and precisely through specific chemical reactions. Success in the synthetic production of elisabethin A would not only represent a breakthrough in chemistry but would also open new perspectives for biological research. For example, it would be possible to investigate for the first time whether elisabethin A is potentially of interest for medical applications. In close cooperation with biochemists, the aim is to examine whether this substance is suitable for the development of new medicines. In addition, our method offers the opportunity of producing similar compounds with a slightly different structure. This would make it possible to better understand structure-activity relationships and discover potential new active substances. Although it was not possible to fully synthesize elisabethin A at the end of the project, it was shown that the developed strategy is suitable for building the complex core structure of elisabethin A. The future research of Thomas Magauer's research group will focus on successfully synthesizing elisabethin A and subsequently investigate its biological properties.