Elements of Synthesis Planning

Book Preface

Synthesis is at the core of organic chemistry. In order for compounds to be studied—be it as drugs, materials, or because of their physical properties— they have to be prepared, often in multistep synthetic sequences. Thus, the target compound is at the outset of synthesis planning.

Synthesis involves creating the target compound from smaller, readily available building blocks. Immediately, questions arise: From which building blocks? In which sequence? By which reactions? Nature creates many highly complex “natural products” via reaction cascades, in which an assortment of starting compounds present within the cell is transformed by specific (for each target structure) combinations of modular enzymes in specific sequences into the target compounds [1, 2]. To mimic this efficiency is the dream of an ideal synthesis [2]. However, we are at present so far from realising such a “one-pot” operation that actual synthesis has to be achieved via a sequence of individual discrete steps. Thus, we are left with the task of planning each synthesis individually in an optimal fashion.

Synthesis planning must be conducted with regard for certain specifications, some of which are due to the structure of the target molecule, and some of which relate to external parameters such as costs, environmental compatibility, or novelty. We will not consider these external aspects in this context. Planning of a synthesis is based on a pool of information regarding chemical reactions that can be executed reliably and in high chemical yield. However, systematic planning of syntheses may in turn identify new types of reactions that would be worthwhile to develop.