Final Report Summary - ROSEPOT (Revolutionising Organic Synthesis: Efficient One-Pot Synthesis of Complex Organic Molecules for Non-Experts)
Nature has evolved highly sophisticated machinery for organic synthesis many of which resemble molecular assembly-line processes. So far chemists have been able to apply this type of approach in the synthesis of peptides and oligonucleotides but in these reactions, simple amide (C‒N) or phosphate (P‒O) bonds are created. It is much more difficult to make C‒C bonds but this is central to the discipline of organic synthesis. This difficulty is why organic synthesis is challenging and why robust, iterative or automated methodologies have not yet emerged. In this grant we developed a reagent which inserts into C-B bonds with exceptionally high fidelity and stereocontrol. As with peptide/oligonucleotide synthesis, the process can be repeated iteratively and in one pot, enabling molecules to be essentially grown. The process converts simple starting materials into complex molecules with specific shape and functionality, key features that are responsible for the properties of a molecule. We have applied this strategy to the synthesis of both natural products and non-natural products. In the latter case, we asked the question why Nature inserts seemingly innocuous methyl groups along carbon chains and what their role might be. By using our iterative homologation process we were able to create carbon chains with just methyl groups attached with specific stereochemistry, and from careful analysis we discovered that their role is to control the shape of the molecule. Thus depending just on stereochemistry, the carbon chain adopted different shapes - helical or linear.
This is the stand-out achievement of the project. Imagine in the future, being able to go to a machine, load a boronic ester, press a few buttons and come back later to unload and purify a complex organic compound which could be a natural product, pharmaceutical or material. Then by pressing a few different buttons or changing the order of the ones pressed before, a related analogue would be produced instead. Such technology would undoubtedly find wide usage in the academia and industry. Our achievements represent a first step towards that goal.
This is the stand-out achievement of the project. Imagine in the future, being able to go to a machine, load a boronic ester, press a few buttons and come back later to unload and purify a complex organic compound which could be a natural product, pharmaceutical or material. Then by pressing a few different buttons or changing the order of the ones pressed before, a related analogue would be produced instead. Such technology would undoubtedly find wide usage in the academia and industry. Our achievements represent a first step towards that goal.