Organic Synthesis Search
Browse synthetic transformations by the desired bond formation
The graphical index, with various options and links to follow, should help in developing new ideas. Please try to search the site directly if you do not find your desired reaction.
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Target-oriented synthesis (TOS) versus diversity-oriented synthesis (DOS)
TOS and DOS are two very different approaches to organic synthesis, with different aims and scopes. If a specific target molecule for example offers properties of interest - such as a natural compound with activity against a specific disease - a short, convenient and high-yielding synthesis should be developed, that allows a fast chemical approach to that desired molecule. In this case, a synthetic chemist takes a piece of paper or software and tries to split this large molecule into smaller molecules (disconnections) and repeats that procedure iteratively, until commercially available building blocks result. This careful analysis - which is known as retrosynthesis - might result in several options that lead to the desired molecule. In the forward synthesis starting from the commercially available building blocks, several synthetic steps are then needed until the desired molecule can be isolated. In a linear approach, unpredictable bottlenecks can cause an unwanted return to the synthetic starting point so enough intermediate is available, whereas a convergent approach limits the risk of a total failure, as only a few steps of a branch synthesis must be repeated. Depending on such risks, experienced organic chemists run the first few reactions at a larger scale and store all intermediates, so they can optimize a reaction step if needed.
A totally different approach is diversity-oriented synthesis. In DOS, organic chemists try to use versatile functional groups and let them react with a broad range of substrates, so the products cover a broad chemical space. That include new functionalities with totally different binding properties, ring sizes and 3D configurations. Such libraries, that are often generated in a combinatorial chemistry approach, can be screened against multiple properties (drug activities, physicochemical properties). Molecules that show properties of interest (for example a low IC50 value for the binding affinity against a specific enzyme) then serve as lead compounds. Synthesizing smaller variations of that initial lead structure in parallel syntheses gives an idea about structure and activity relation (SAR) of specific modifications.
If one of these smaller variations results in a more active compound, this molecule becomes the new lead compound. Over the time, the syntheses also become more targeted, as people develop a better understanding of the SAR and focus on specific molecules rather than diversity.