10. Asymmetric Total Synthesis of Complex Marine Natural Products
J. Hassfeld, T. Stellfeld, M. Kalesse, M. Christmann
The synthesis of natural products is one of the most important research topics in organic chemistry [1, 2]. Apart from the more classical fields such as isolation and structure elucidation, a special focus is placed on efficient and selective synthesis of biologically important naturally occurring compounds. On the other hand, the synthesis of complex natural products, which is judged by the highest synthetic standards, can no longer be the sole reason for the initiation of research programs. The variety of different techniques and new methods in organic chemistry allows for synthesizing even the most complex natural products. In this context, the evaluation of biological mechanisms and targets connects synthetic organic chemistry with cell biology. Only the combination of both allows for broadly addressing biological questions such as cell cycle regulation or transport through membranes. In this context, we will focus on marine natural products that offer an extension to the structural diversity of known terrestrial natural products. Furthermore, we will emphasize elegant techniques that allow for the rapid assembly of complex structures in addition to their application in simplifying and deconvoluting structure-activity relationships as a starting point for more detailed biological investigations. All natural products covered herein have unique biological activities and synthetically challenging frameworks. At the beginning of each chapter, we will introduce the reader to their chemical and biological properties and provide a short overview on the status quo. Additionally, the focus on particular transformations allows readers who are not accustomed to synthetic problems to appreciate the covered achievements and to put the retrosynthetic analyses into perspective with the biological properties. The selection of marine natural products covered herein provides examples where synthesis had to overcome shortages of supply from natural sources (leucascandrolide). Modified natural products are the essential tools for target identification (bryostatin), and simplified structures provide a practical access to structures relevant for pharmacology (bryostatin, ciguatoxin).