Are there limits to rational chemical synthesis?

Abstract

Chemical synthesis is the purposeful execution of one or more reactions to obtain a product, or several products, which could modify the existing molecular frameworks, or make a complex (often natural) molecule from simple reagents. There are several possible reasons to make complex molecules by total chemical synthesis. A century ago the aim was often to identify a molecular structure. With the advent of routine X-ray crystallography and high-field FT NMR in the late 1960s, total chemical synthesis served as a necessary structural confirmation became much less compelling. Another reason that chemists synthesized natural products was because of their useful properties. In some cases, molecules could be cheaper to make from scratch than to obtain from nature source. The history of chemistry is essentially the history of finding out the structure of molecules and of developing new and efficient methods of making them. Putting these molecules to new uses is what underpins our modern world, but it was really a secondary goal for most of chemistry’s history. Great synthetic chemists of the mid-to-late twentieth century are revered not so much for what they made but for how they made it. Synthesis cultivates an understanding of the basic principles of chemistry: how and why reactions occur, the relationships between molecular shape and function, and so on. Today, synthetic chemists still need to pursue “ideality” in the way molecules are synthesized, and total synthesis should be able to provide large quantities of complex natural products with a minimum amount of labor and material expense. In future years, the emphasis of synthetic chemistry, also natural product synthesis, will shift from delivering structures to delivering functions. Natural products will continue to serve a central role in the discovery and development of pharmaceutical agents as well as the elucidation of new biological targets of therapeutic relevance. Synthetic chemists are in a unique position to define those very important molecules that we want, which allow us to access to non-natural derivatives that may offer superior biological and physical properties in comparison to the natural material. The research in natural products synthesis has indeed been the impetus for many fundamental discoveries and could also motivate future research in chemistry and biology.