Natural Product Synthesis and Development of Novel Reaction Methodology

Abstract: Popular Abstract in English Organic synthesis has been defined as the “intentional construction of molecules by chemical means”1 and is often regarded to have commenced with Wöhler’s preparation of urea in 1828.2 Today, the influence of organic synthesis reaches far beyond the domain of chemistry, touching upon fields such as biology, nanotechnology, material science, and medicine. It has thus supplied mankind with pharmaceutical drugs for the treatment of numerous health related conditions3 as well as novel materials, dyes, plastics, clothing, perfumes etc.4 Organic synthesis can broadly be divided into two main fields: total synthesis and methodology development. Total synthesis can be regarded as the laboratory construction of organic molecules, often naturally occurring, by means of a series of rationally designed chemical reactions, starting from less complex, often commercially available, starting materials. The creative aspect of this field means it is widely recognized as form of art, manifested in both the delicate selection of chemical operations and the target structure itself. To enable such total synthesis endeavors requires an extensive repertoire of chemical reactions, and an understanding of how these can be combined to successfully reach the target structure. The other cornerstone of organic synthesis therefore deals with the development of novel and increasingly efficient reaction methodology. There are several valid incentives to prepare new or naturally occurring chemical entities. Since isolation from natural sources can often provide only minute quantities, accessing the compound through total synthesis is sometimes the only means by which to obtain large enough quantities for biological evaluations. Such studies may provide valuable intermediates for a host of different investigations, ranging from toxicological and pharmacological evaluations to elucidation of biochemical and metabolic pathways.5 An additional impetus for total synthesis is the possibility to access analogues or isomer of naturally occurring compounds, which can be used to establish structure activity relationships or probe biological mechanisms.6 Sometimes, the complexity and intellectual challenge associated with a certain problem is a contributing reason to pursue a synthetic endeavor, at least within the realm of academia. Such reasons are by no means invalid, since curiosity and intellectual challenge has always been at the heart of scientific discovery. Although total synthesis and methodology development are two distinctly different fields, they are also closely connected. The strength of a particular transformation is often highlighted by its application in total synthesis, which in turn sometimes leads to fortuitous discovery of novel reactivity that can be further developed into new reactions.