Design of bio-inspired materials and total synthesis of "Securinega" alkaloids

This thesis is divided into four chapters presenting distinct research projects that address challenges in the fields of functional systems chemistry, chemical biology, and the total synthesis of natural products. Experimental details, analytical data and appendices are enclosed at the end of this work.
Chapter 1 introduces the concept of electron-poor catechols as surface binding agents and highlights some of the natural role models. The development of a synthetic surface modification platform for the controlled release of small molecules is described. Nitrocatechol-based anchoring units allowed for the immobilization of a molecular cargo on titanium dioxide surfaces and cleavage on demand by UV irradiation.
Chapter 2 expands the application of small catechol binders. The design and synthesis of new polar derivatives facilitated the use of boronate esters in dynamic functional systems and led to the discovery of the third orthogonal dynamic covalent bond.
Chapter 3 reports on the preparation of biochemical probes for the investigation of the cellular target of rapamycin. An efficient assembly of natural product hybrids from rapamycin was achieved without the need for protection of the macrolide. The antiproliferative activity of the parent compound was shown to be largely conserved in the novel substances.
Chapter 4 provides a detailed review of the literature on Securinega alkaloids. The first enantioselective total synthesis of secu’amamine E was accomplished in twelve linear synthetic steps and 8.5% overall yield. Three examples of an intriguing rearrangement process were studied allowing for the direct interconversion of natural products with implications for a new biogenetic hypothesis.