ISBN 9783843910972

978-3-8439-1097-2, Reihe Organische Chemie

Johannes Hoecker
Stereoselective Total Syntheses of Piericidins, the Neuritogenic Steroid Withanolide A and the Development of Photolabile Surface Anchors

230 Seiten, Dissertation Universität Basel (2013), Softcover, A5

Zusammenfassung / Abstract

This thesis includes a detailed description of the stereoselective synthesis of the neuritogenic steroid lactone withanolide A. Key for the successful total synthesis were mostly strategic considerations for the sequential order of the installment of the enone moiety. The total synthesis was achieved by singlet oxygen Schenck ene-reaction, Wharton transposition, a Corey-Seebach homologation and a vinylogous aldol reaction. Biological evaluation demonstrated neurite outgrowth, which further supports the potential neuritogenic role of this compound in traditional Indian medicine.

In addition, the first total syntheses of the piericidin natural products JBIR-02 and Mer A2026B, and related piericidins are reported. Key features of the unified synthetic strategy involved an Ir-catalyzed one pot C-H activation/oxidation procedure for the preparation of multiple hydroxypyridines, a vinylogous Mukaiyama aldol reaction and a Negishi cross-coupling of an advanced pyridine intermediate with the fully elaborated allylic side chain. Following the successful total synthesis, the absolute configurations of Mer A2026B and JBIR-02 were established as (9R,10R).

Further the development of a molecular surface modification platform based on biomimetic nitrocatechol derivatives is reported. This allowed for small molecule functionalization under mild aqueous conditions and efficient release triggered by light therefore uncaging a small molecule cargo on demand. Small molecules may be fluorescent marker as shown in the proof-of-principle study or bioactive small molecules for drug release.

Keywords: Natural Products, Total Synthesis, Neurite Outgrowth, Photocleavable Surface Hybrids, Steroids, Piericidins, Retinoids and Bipyridines