Investigation Towards the Total Synthesis of Portentol <em>via</em> an Inverse Electron Demanding Diels Alder Reaction and Studies Towards the Total Synthesis of Brevistin

Abstract

The first chapter of this doctoral thesis explores the potential for a total synthesis of portentol through an inverse electron demanding Diels-Alder (IEDDA) reaction. Although, Trauner et al. had previously developed a total synthesis for portentol it continues to be an intriguing synthetic target. This is attributed to its potential bioactivity towards cancer cell lines and Mycobacterium tuberculosis. Furthermore, portentol features eight stereocenters condenses into a bicyclic spiro structure, making it a perfect candidate for the Diels-Alder reaction. This reaction is renowned for its ability to introduce stereocenters, create a double bond, and form a six membered ring in a single step. Additionally, achieving exo selectivity in the IEDDA reaction is essential to obtain the desired stereoselectivity, which poses an intriguing challenge due to the well known endo selectivity of the Diels-Alder reaction. <br> The second chapter of this dissertation delves into brevistin, which was initially isolated in 1975 from the bacterium Bacillus brevis 342-14. Brevistin is a cyclic lipopeptide comprising 11 amino acids and a fatty acid chain. It exhibits antibiotic activity against Gram positive bacteria, including bacterial strains such as Streptococcus pyogenes, Staphylococcus aureus and Streptococcus pneumoniae. To further investigate its antibiotic activity it serves as an appealing target for total synthesis and presents the potential for derivatization to enhance its biological characteristics.