University thesis:
Dissertation, Friedrich-Schiller-Universität Jena, 2023
Footnote:
Tag der Verteidigung: 24.04.2023
Description:
Sphingolipids are found in mammalian and bacterial membranes where they exert multiple intra- and intercellular functions. Therefore, binding partners of sphingolipids provide excellent targets for therapeutic approaches. Structurally related sulfonolipids (RIFs) are also of great interest for the interspecific interaction of Salpingoeca rosetta. In the present work, new access routes to both classes of compounds are demonstrated by the means of total chemical synthesis. Using a hydrozirconation/transmetallation reaction and a three-step one-pot reaction protection/deprotection sequence, several unnatural 2S,3S-6-hydroxy-4E-sphingenin-containing sphingolipids were prepared in only three (protected) or four (fully deprotected) consecutive synthetic steps. Among them is a fluorescently labeled derivative suitable for future biological studies. Furthermore, the first total synthesis of two RIF-2 diastereomers and one congener is reported, using 15 and eight synthetic steps, respectively. A decarboxylative cross-coupling reaction is used to synthesize the required branched alpha-hydroxy fatty acids. Furthermore, three different strategies are discussed in terms of their suitability for the synthesis of sulfonolipids: 1) the "cysteine" strategy, which uses cysteine as the central building block; 2) the "thioligation" strategy, which provides for a reaction similar to native chemical ligation to generate the peptide bond; and 3) the "late stage" strategy, which provides for the introduction of sulfur at the end of the total synthesis. Finally, the synthetic compounds are compared to the natural isolates in terms of their properties.