The achievements awarded the 1990 Nobel Prize in Chemistry demonstrate how the secret to constructing synthetic versions of chemicals from scratch is to work backwards. Elias Corey developed and refined a novel, reverse approach to synthesizing organic compounds – that is, compounds that contain carbon atoms – and in the process he transformed this discipline from an art into a more logical and systematic process.
When Corey began his career in the 1950s, creating synthetic versions of organic compounds was carried out on a case-by-case basis, and relied largely on trial and error. Skilled exponents, such as Robert Woodward, who received the 1965 Nobel Prize in Chemistry, built compounds of a complexity unseen at the time by spotting possible starting subunits within the structure of a chemical, and devising ways in which to tweak and manipulate these subunits to generate the complete molecule. Corey, on the other hand, believed in a more rational approach that began with the theoretical structure of the end product. By strategically breaking key bonds within the complete molecule, he envisaged how it could be split into progressively simpler fragments until one is left with fragments that are already known and available in the laboratory, from which the building process could begin.
Corey formulated a set of general principles and guidelines, which he termed retrosynthetic analysis, to logically determine how best to break up any complex compound into simple precursor fragments and to work out the best path to constructing them from starting materials. Putting his own theories into practice, Corey devised routes for successfully synthesizing over 100 compounds; perhaps the most notable being his construction of synthetic versions of prostaglandins, which are involved in a host of important biological processes, including the regulation of blood pressure and the heart. When chemists were limited by the existing synthetic reactions that they had in their chemistry set to reconstruct fragments, Corey developed a series of new reactions that could force fragments together in different ways. Eventually computer programs were created using Corey’s principles and guidelines, allowing chemists to design new molecules and pinpoint the simplest possible paths for synthesizing them.