ISBN 9783843946988

978-3-8439-4698-8, Reihe Organische Chemie

Ömer Taşpınar
Synthesis of Marine Steroids with Unusual Ring Systems: Eurysterol A and DELTA24-Dihydro-6-epi-Monanchosterol A and Total Synthesis of Houttuynoid B-Derivatives as Potential Antiviral Agents

268 Seiten, Dissertation Universität Köln (2020), Hardcover, A5

Zusammenfassung / Abstract

Eurysterol A, a cytotoxic and antifungal marine steroidal sulfate with a unique C8–C19 oxy-bridged cholestane skeleton, was isolated in 2007 from a sponge of the genus Euryspongia collected in Palau. The compound was found to display cytotoxicity against HCT‐116 human carcinoma cells as well as antifungal properties against amphotericin B‐resistant strains of Candida albicans. Structurally, the eurysterols are characterized by an unusual 8,19-epoxy cholestane skeleton with a sodium sulfate group at C3 and a 5α,6β-diol moiety. This work describes the first chemical synthesis of eurysterol A. As a key step, an intramolecular oxa-Michael addition was exploited to close the oxy-bridge (8β,19-epoxy unit). Along the optimized (scalable) synthetic sequence, the target natural product was obtained in only 11 steps in 5% overall yield. Furthermore, a first synthetic entry towards the monanchosterols, a new class of natural products possessing a steroid-analogue structure with a characteristic bicyclo[4.3.1]decane A/B ring system was developed, via intramolecular aldol reaction of a 5,6-secosterol. The elaborated access to the core structure of monanchosterols with a Δ24-saturated cholesterol side chain represents the basis for future studies towards synthesis of the natural monanchosterols and the evaluation of their biological potential. The second part of this thesis describes the synthesis of analogs of the antiviral natural houttuynoid B with different sugar moieties and side chains. Previously, it was found that a synthetic derivative of houttuynoid B (TK1023), which differs only by acetylated glycoside moiety, prevents cell entry of Zika virus. The synthesized analogs, which are currently under biological investigation, will contribute to the understanding of structure-activity relationships (SAR) of this promising class of antiviral flavonoid glycosides.