How it works: organic synthesis

Organic synthesis

Organic synthesis is a branch of chemical synthesis concerned with constructing organic molecules. A one- or two-step sequence for a simple modification of a molecule is not that difficult to deduce but there is often more than one effective procedure that leads to the desired product. This is even more the case with increasing sequence length and growing complexity of target molecules. With so many possibilities, a chemist needs to carefully analyse the options regarding scope, constraint and limitations of each individual step, while keeping the overall pathway in mind. Indeed, one single choice made at the beginning may interfere with a reaction many steps further down the path. In fact, the more steps required to synthesise a molecule, the more the pathways resemble a maze. Sometimes, not even the easiest step in theory also works under laboratory conditions. E.J. Corey brought a more formal approach to designing a chemical synthesis and formulated a technique known as retrosynthetic analysis for which he won the Nobel Prize in Chemistry 1990. Recent research aims at computer-assisted synthetic analysis and design, which is becoming ever more efficient and accurate by using machine learning.

Furthermore, an organic synthesis does not need to be linear but can consist of several key pieces that are combined for the final product. This so-called “convergent synthesis” has the advantage of generating a higher yield. Not only should a synthesis be feasible in the lab, it should theoretically be as short and high-yielding as possible, while keeping the chemistry and lab work simple and the cost low. In practice, a balance needs to be found between these aspects in order, for example, to lead to a longer but higher-yielding synthesis.

As for what happens in the lab, time is spent not only on setting up reactions and following their course, but also on isolating and purifying the reaction product. When working with dye molecules, the isolation procedure can be quite colourful (see picture above).

Céline Schuppisser
NCCR TransCure PhD student in J.-L. Reymond group