Periodic Reporting for period 1 - CF3-DIAZOMETHYLATOR (Photocatalytic C–H Bond CF3-diazomethylation)
Okres sprawozdawczy: 2018-03-01 do 2020-02-29
Over the last century, the pharmaceutical industry successfully commercialized numerous synthetic drugs in the form of small molecules for the treatment of a wide range of diseases. The commercialization of a new drug typically encompasses several phases: (a) drug discovery (preparation of 10,000-15,000 compounds), (b) pre-clinical phase (250 compounds), (c) clinical phases (5 compounds), (d) regulatory approval and market (1 compound).
In the drug discovery phase, organic synthesis proved itself as an enabling tool for the preparation of a wide range of diverse chemical entities. Indeed, very small structural changes in the molecular formula of a chemical compound can dramatically influence its biological or therapeutic activity. Synthetic tools are consequently of utmost importance in the drug discovery process, especially when considering that it typically requires that one out of 15,000 compounds usually make it to the market. As a general trend, the higher the number of compounds in drug discovery the higher the probability of success. This means that, to get one approved drug, multiple molecules are put into clinical development, requiring large expenses spent on R&D. These statistics call for the discovery of new chemical reactions able to reach large but unique chemical space only limited by the imagination of the scientist. In particular, strategies to create molecular diversity at advanced stages of the synthesis is highly attractive, as a large chemical space becomes in reach with a minimal effort, which allows decreasing both the cost and the time of the discovery of new lead compounds for certain therapeutic applications.
The discovery of fundamentally-new chemical reactions able to reach a unique chemical space in a cost and time efficient manner is highly relevant to the mission of inventing new medicines to improve the lives of patients or to fulfill an unmet medical need. A current example is the need to discover live-saving therapeutics based on small-molecules to cure infected patients with SARS-CoV-2.
This project pretended to discover new chemical reactions based on the catalytic generation of equivalent forms of carbyne equivalents and explore their application in transforming simple into complex molecules, late-stage functionalization of complex molecules and explore radiolabeling applications.
In the drug discovery phase, organic synthesis proved itself as an enabling tool for the preparation of a wide range of diverse chemical entities. Indeed, very small structural changes in the molecular formula of a chemical compound can dramatically influence its biological or therapeutic activity. Synthetic tools are consequently of utmost importance in the drug discovery process, especially when considering that it typically requires that one out of 15,000 compounds usually make it to the market. As a general trend, the higher the number of compounds in drug discovery the higher the probability of success. This means that, to get one approved drug, multiple molecules are put into clinical development, requiring large expenses spent on R&D. These statistics call for the discovery of new chemical reactions able to reach large but unique chemical space only limited by the imagination of the scientist. In particular, strategies to create molecular diversity at advanced stages of the synthesis is highly attractive, as a large chemical space becomes in reach with a minimal effort, which allows decreasing both the cost and the time of the discovery of new lead compounds for certain therapeutic applications.
The discovery of fundamentally-new chemical reactions able to reach a unique chemical space in a cost and time efficient manner is highly relevant to the mission of inventing new medicines to improve the lives of patients or to fulfill an unmet medical need. A current example is the need to discover live-saving therapeutics based on small-molecules to cure infected patients with SARS-CoV-2.
This project pretended to discover new chemical reactions based on the catalytic generation of equivalent forms of carbyne equivalents and explore their application in transforming simple into complex molecules, late-stage functionalization of complex molecules and explore radiolabeling applications.
We have unveiled the catalytic generation of metal-carbynoids and discovered a previously-elusive C–C bond cleavage. These reactive species offer a new logic in chemical synthesis and the process developed underscores an opportunity as a tool in skeletal editing that is relevant to reach previously unattainable chemical space in drug discovery. This work was published in the Journal of the American Chemical Society in open access and was among the most read articles in September 2019. Previous to its publication, the ER presented part of this work in a major European congress dedicated to Frontiers in Organic Chemistry. Moreover, due to the novelty and potential broad impact of this concept, it was highlighted in Chemistry Views & Chemistry World. Along the MSCA period, the ER has been able to discover other valuable transformations with promising scope and applications, attend other congresses and present posters and deliver short talks.
The MSCA project has allowed to the ER to become an excellent scientist that that will lead him to an independent academic position. Being exposed to cutting-edge research in a world-class research institution has provided him exceptional opportunities for the development of his research experience, professional maturity, diversity, independence, and leadership qualities. His discoveries at ICIQ will allow him to be recognized among the broad synthetic community in the academic and private sectors. The new synthetic tools discovered by the ER has opened a new research line in the host group and the applications in drug discovery and diagnosis are being studied. A number of pharmaceutical industries have shown interested in the technology and in its potential impact to accelerate the drug discovery process.