Objective The creation of new molecular entities and subsequent exploitation of their properties is central to a broad spectrum of research disciplines from medicine to materials but progress has been limited by the difficulties associated with chemical synthesis. We are now proposing a fundamentally new strategy, which has the potential to revolutionise how we conduct complex organic synthesis. The basic C–C bond-forming step involves the reaction of a lithiated carbamate with a boronic ester to give a homologated boronic ester with complete stereocontrol. Furthermore, the reaction shows >98% efficiency in most cases and can be conducted iteratively and in one pot (up to 9 iterations has been demonstrated with full stereocontrol). We will now extend this methodology to more functionalised carbamates as this will enable the rapid synthesis of polypropionates, which are amongst the most important classes of biologically active molecules. The robust methodology is now ripe for transfer to the solid phase as this will enable the preparation of libraries of these molecules. Through applying our assembly-line-synthesis methodology to complex molecules with diverse structures, we will demonstrate its scope, robustness, and full potential. The methodology enables stereochemistry to be ‘dialled in’ to a carbon chain, which in turn controls the conformation and we will exploit this feature in the shape-selective synthesis of molecules. We will explore how the sense of helical chirality of these molecules can be switched (M to P) just with light. We will target helical molecules with specific groups at specific places for optimum binding to disrupt protein–protein interactions involved in cancer. Finally, our methodology provides ready access to a family of building blocks that represent common repeat units found in polyketides. By combining these building blocks iteratively using lithiation-borylation, we should be able to rapidly and reliably prepare complex natural products. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural scienceschemical sciencesorganic chemistryorganic acidsnatural scienceschemical sciencesorganic chemistryalcoholsnatural scienceschemical sciencesinorganic chemistrymetalloidsnatural scienceschemical sciencesorganic chemistryamines Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-ADG-2014 - ERC Advanced Grant Call for proposal ERC-2014-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator UNIVERSITY OF BRISTOL Net EU contribution € 2 436 379,00 Address Beacon house queens road BS8 1QU Bristol United Kingdom See on map Region South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITY OF BRISTOL United Kingdom Net EU contribution € 2 436 379,00 Address Beacon house queens road BS8 1QU Bristol See on map Region South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bristol, City of Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
