Descrizione del progetto
Nuovi metodi di sintesi delle molecole chirali potrebbero aumentare la sostenibilità della scoperta dei farmaci
Più della metà dei farmaci attualmente in uso è rappresentata da composti chirali. Nonostante gli enormi progressi compiuti sulla catalisi negli scorsi decenni, la «complessità chirale» delle librerie chimiche nella scoperta dei farmaci non ha seguito la stessa tendenza al rialzo. L’industria farmaceutica ha estremamente bisogno di processi efficienti che accedano direttamente a substrati chirali privilegiati. Le reazioni di accoppiamento incrociato di alcheni e legami C-H arilici aggirano le fasi di «concessione» intraprese da altre reazioni accoppiate incrociate utilizzate nell’industria farmaceutica, riducendo così al minimo costi, sforzo e scarti. Il progetto ChiCC, finanziato dall’UE, svilupperà catalizzatori adeguati per queste reazioni accoppiate incrociate che incoraggino le formazioni di legami C-C, concentrando l’attenzione su una maggiore step economy. Gli scienziati utilizzeranno inoltre reazioni con un’elevata atom economy, fondamentale per la sostenibilità dei processi chimici.
Obiettivo
Over 60% of the world’s top selling small molecule drug compounds are chiral and, of these, approximately 80% are marketed as single enantiomers. Surprisingly, and despite the tremendous advances made in catalysis over the past several decades, the average “chiral complexity” of drug discovery libraries has actually decreased, while, at the same time the “chiral complexity” of marketed drugs has increased. Consequently, there is now an urgent need to provide efficient processes that access directly privileged chiral “3D” building blocks. It is our philosophy that catalysis holds the key here and new processes should be based upon atom and step economical platforms that exert control over both absolute and relative stereochemistry. Palladium catalysed cross-coupling reactions of aryl (pseudo)halides with organo-nucleophiles (esp. the Suzuki coupling) have become mainstays of the pharmaceutical industry. Here, multiple “concession” steps are usually required to prepare the reaction partners, thereby detracting from atom and step economy. Further, these processes predominantly provide planar “2D” structures and are not well suited to the production of chiral “3D” building blocks. Consequently, methods that allow feedstock precursors (e.g. alkenes and aryl C-H bonds) to be combined directly in enantioselective or enantiospecific C-C bond formations are highly desirable. Cross-couplings of this type would circumvent “concession” steps, thereby minimising cost, effort and waste; however, such processes are highly challenging because of issues associated with regio- and stereocontrol. Recently, we developed prototype catalyst systems that can address this. In the proposed ERC project, these exciting preliminary results will be developed into a wider family of processes where asymmetric C-C bond formations are achieved directly by C-H activation. The new methods, which fulfil modern reaction ideals of atom and step economy, will likely find broad use in applied settings.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
L69 7ZX Liverpool
Regno Unito