Structure Elucidation of Mytilipin B

Abstract

The chlorosulfolipids comprise a relatively small class of natural products isolated from aquatic organisms. As structural motifs, they share extensive chlorination of an aliphatic backbone along with further functionalization leading to densely functionalized aliphatic structures. The to-date most complex chlorosulfolipid isolated is Mytilipin B, reported in 2002 after isolation from a toxic batch of the culinary mussel Mytilus galloprovincialis. It is assumed that Mytilus galloprovincialis accumulates Mytilipin B through consumption of the original producer and does not produce Mytilipin B itself impeding reisolation. Complete structural assignment of Mytilipin B by NMR was followed by a total synthesis that uncovered the originally assigned structure to be incorrect and the originally obtained spectral data had been lost. In the first part of this thesis, a detailed investigation of published information on Mytilipin B is described to reassign its chemical structure. This was corroborated by synthetic efforts that led to syntheses of four diastereomers and eventually to synthetic, revised Mytilipin B. Furthermore, spectral data was collected and interpretated to determine the dominant solution state conformation of Mytilipin B, shedding light onto its proposed role as a membrane lipid. Janustatin A is a polyketide natural product isolated in 2019 from the culture broth of Gynuella sunshinyii YC6258T. During biological testing against numerous cell lines, potent cytotoxicity was observed against all tested strains. This biological activity along with an uncertain structural assignment rendered Janustatin A a tantalizing target for total synthesis. In the second part of this thesis, the first total synthesis of Janustatin A is presented. Varioxepine is an oxepine-containing diketopiperazine-type alkaloid isolated from the endophytic fungus Paecilomyces variotii. This natural product exhibits interesting antibacterial and antifungal inhibitory potency against diverse organisms, amongst them the economically devastating plant-pathogenic fungus Fusarium graminearum. Additionally, the rare oxepine and orthoamide motifs render Varioxepine a synthetically challenging target for an organic chemist. The third part of this thesis describes studies towards a total synthesis of this natural product.