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Timing is key: Late-stage nitrogen insertion enables better heterocycle syntheses
To facilitate the synthesis of new molecules that could serve as active pharmaceutical ingredients, Professor Dr. Johannes Wahl, a scientist in the Department of Chemistry at Johannes Gutenberg University Mainz (JGU), has been awarded funding from the European Union. The European Research Council (ERC) is supporting his project "Molecular Editing by Nitrogen Insertion – NINSERT" with a Starting Grant worth around EUR 1.5 million. ERC Starting Grants are designed to help researchers at the beginning of their careers establish independent research groups and solidify their positions. The funding is set for five years. The goal of the NINSERT project is to streamline the synthesis of nitrogen-containing compounds, accelerating the identification of promising drug candidates and tailoring their properties.
NINSERT – a program for selective and mild nitrogen insertions
Nitrogen (N) is the predominant element in the atmosphere, and it is also essential for life as a key component of proteins. However, nitrogen also appears in about 60 percent of all low-molecular-weight drugs, which make up the majority of all approved medications. In these drugs, nitrogen heterocycles determine the properties of the molecule to a large degree. This underscores the importance of the funded project for future pharmaceutical research. "Nitrogen heterocycles are fascinating compounds. They occur in many natural products and, because of their advantageous properties, are also found in the most widely used drugs," said Wahl. "In this research project, we will focus on synthesizing promising candidates using new methods."
Historically, many different synthetic methods have been developed to access heterocycles, according to Wahl. Heterocycles are organic compounds with a cyclic structure that includes at least one element other than carbon – in this case, nitrogen. Over a century ago, German chemists Ernst Beckmann and Karl-Friedrich Schmidt pioneered work in this field. However, despite their methods still being used today, they face significant limitations. "The available starting materials are limited, the conditions for chemical reactions are harsh, and the results are often unspecific," explained Professor Johannes Wahl.
Nitrogen insertion as a late-stage chemical step
Within the NINSERT project, Wahl and his team will explore, develop, and test powerful tools to improve the synthesis of nitrogen-containing compounds. Whereas nitrogen is usually introduced early within a synthetic sequence, late introduction requires further research. "We need new reagents and milder conditions," said Wahl. "This will allow us to specifically modify the core structures and significantly speed up the synthesis of new candidates." Late-stage nitrogen insertion allows for better adjustment of the physical and chemical properties. Recently, the concept of inserting nitrogen has gained momentum in organic chemistry. Wahl has been working in this area for about five years and is one of the leaders in the field.
Born in 1989, Johannes Wahl studied chemistry and joined the Novartis Institute of Biomedical Research in Switzerland after completing his Master's degree in 2012. He completed his Ph.D. in organic chemistry at the Technical University of Munich (TUM) from 2013 to 2016 and then worked as a postdoc at Indiana University in the USA. Since 2020, he has held a junior professorship in the Department of Chemistry at JGU. In Mainz, Wahl has access to the exceptional scientific resources and analytical facilities of the Department of Chemistry.
ERC Starting Grants support promising ideas of young researchers
The ERC Starting Grant is one of the most highly endowed funding programs of the EU awarded to young scientists. ERC Starting Grants support outstanding researchers at the beginning of their careers as they build their own research programs. In addition to demonstrating scientific excellence, applicants must prove the groundbreaking approach and feasibility of their projects to receive funding.
Images:
https://download.uni-mainz.de/presse/09_wahl_johannes.jpg
Professor Dr. Johannes Wahl (©: private)
https://download.uni-mainz.de/presse/09_chemistry_nitrogen-insertion.png
The NINSERT project aims to break new ground in drug development by late-stage nitrogen insertion. (ill./©: Johannes Wahl)
Related links:
• https://www.wahllab.com/ – Research group of Professor Johannes Wahl at the JGU Department of Chemistry
Junior Professor Dr. Johannes Wahl
Preparative Organic Chemistry
Department of Chemistry
Johannes Gutenberg University Mainz
55099 Mainz, GERMANY
phone: +49 6131 39-23242
e-mail: wahl@uni-mainz.de
https://www.wahllab.com/johannes-m-wahl
Professor Dr. Johannes Wahl
©: private
The NINSERT project aims to break new ground in drug development by late-stage nitrogen insertion.
ill./©: Johannes Wahl
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