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.
