Link: cordis.europa.eu/project/id/101142915
Duration: 01.01.2025–31.12.2029
Funding amount: € 2.750.000 
Keywords: organic synthesis, charge control, functionalisation, hydride, proton
Abstract
Organic synthesis stands as the beating heart of technological and societal advancement, driving breakthroughs in drug discovery, agrochemistry, materials design, and the pursuit of a more sustainable world. In a world where C–H bonds are the main functional groups available, the field of C–H functionalisation has experienced exponential growth over the past two decades. While state-of-the-art methods have led to remarkable achievements, they remain confined by the dominance of substrate-controlled reactions driven by directing group logic, and by being largely reliant on precious metal catalysts. 

C-HANCE proposes to open a new page in C–H functionalisation, exploiting the emerging concept of charge control as a mode to influence and steer reactivity of C–H bonds. This will usher in a new logic for C–H bond functionalisation, where reagent control can address substrates devoid of directing groups and where entirely novel reactions will emerge. This will not only reshape our fundamental understanding of C–H functionalisation, but also yield valuable products for downstream applications.

Link: projekte.ffg.at/projekt/5132494
Duration: 02.12.2024–01.12.2028
Project Partners: TU Wien, Boehringer Ingelheim RCV GmbH & Co KGProf. Harald H. Sitte (Medical University of Vienna)
Keywords: Grüne Chemie; Bildungsinitiative; Nachhaltige Chemie; Synthese; Biotechnologie; Verfahrenstechnik 
Abstract
The program GreenChem-TechHub focusses on PhD education at the cross-roads of science and economy. Participating PhD projects focus on research questions in the area of green chemistry and range from innovative concepts in feedstock valorization, waste-stream exploitation, chemical modification of biogenic materials to synthetic method development for high-value chemical production in pharmaceutical industry. Applied methods include biotechnology, organic synthesis, and chemical engineering. Key role of the technology hub relates to enhancing inter-disciplinary exchange, maximize synergies, and empower core expertise of participants in the field of green chemistry; by this, know-how transfer of participating industry partners shall be facilitated. Participating coworkers conduct research both at industry partners as well as at the involved academic institutions to ultimately achieve a PhD degree. Know-how exchange and tight interaction between researchers is enabled by structured educational incentives in order to achieve a competitive expert level in green chemistry for subsequent career stages.
The structured complementary training program within the PhD school will result in the following qualification profiles:
• Establishing core expertise and a pool of excellently trained personnel in green chemistry.
• Close cooperation and exchange of expertise between participating academic and industry partners.
• Empowering research careers in industry releated research and development.

Link: www.fwf.ac.at/forschungsradar/10.55776/P37182
Duration: 01.03.2024–29.02.2028
Funding amount: € 399.346
Keywords: Hydride Shuttle, Alkaloids, Synthetic Methods, Redox Isomerisation, Multicomponent Reactions 
Abstract
While the function of chemical structures is not inherently based on their complexity, with many successful pharmaceuticals being rather simple compounds, more elaborate structures hold much promise. Particularly, even slight alterations to chemical structure can elicit profound changes in biological activity. Among such compounds, those containing nitrogen atoms within a cyclic structure are particularly interesting and the development of more efficient syntheses remains of the highest importance. Drawing on the foundation laid by previous work developed in our group, we propose the development of a range of new reactions, which are based on a concept termed inverse hydride shuttle catalysis. This concept underpins a spectrum of novel reactions designed to yield a diverse array of products. Yet, while potentially giving access of a wide variety of different products, our proposed reactions can be comprehensively categorized as i) taking advantage of the rapid aggregation of simple, and often commercially available, starting materials, ii) employing metal-free catalysts for the selective modification of nitrogen-containing structures and iii) delivering (poly)cyclic compounds with high complexity. Although the foundational principles of this concept have been elucidated in earlier work, our proposed endeavors aim to extend and generalize this process. Integration with other reactions is pivotal, promising the generation of heavily functionalized products with versatile applications across various fields. The envisioned outcome is a streamlined and versatile methodology that capitalizes on the "inverse hydride shuttle catalysis" framework, and will give rise to much more heavily functionalized products with potential applications in a wide variety of fields. This research project aspires to position "inverse hydride shuttle catalysis" as a universally applicable method, offering researchers across natural sciences and beyond a tool for the rapid synthesis of structures that were once beyond reach. The prospect of facilitating the exploration of uncharted chemical territories underscores the broader impact of this methodology, transcending disciplinary boundaries and contributing to the advancement of scientific knowledge.

Link: www.fwf.ac.at/forschungsradar/10.55776/PAT1509823
Duration: 01.07.2024–31.12.2026
Funding amount: € 485.060
Project Partner: Prof. Harald H. Sitte (Medical University of Vienna)
Keywords: Amphetamine, Partial Releaser, Amines, Hydroaminomethylation, Pharmacology
Abstract
Wider research context: Structural modification of established bioactive compounds, as enabled by synthetic chemistry, holds the potential to change efficacy or target, thereby offering an opportunity to study alternative therapeutic strategies. In this regard, the countless established amphetamine derivatives have shown that alterations to the substitution pattern often elicit dramatic changes to the biological function. Initial results from our team indicate that, contrary to previous reports of inefficacy, homologation of the amphetamine chain may be capable of inducing partial efficacy at monoamine transporters (MATs).
Hypotheses and objectives: We will employ our original method to synthesize a wide range of homologated amphetamines (homoamphetamines), ultimately allowing us to study their releaser activity at monoamine transporters. Based on initial results, our hypothesis is that this variation to the core amphetamine structure holds the potential to create partial releasers, resulting in opportunities to fine-tune transporter-mediated efflux and maximize possible therapeutic efficacy. Crucially, further development of a previously reported amine synthesis through an alkene hydroaminomethylation reaction is necessary to introduce new structural motifs. We have also obtained initial evidence that the stereochemistry of homoamphetamines affects efficacy. For this reason, we aim to establish a novel, enantioselective approach to hydroaminomethylation, to aid in the study of stereochemical effects.
Approach and methods: We will combine several methods and approaches in an iterative strategy: organic synthesis will produce an array of diversely substituted homoamphetamines (including enantioselective synthesis), followed by a number of experimental in vitro approaches. Here, mainly tracer flux assays, electrophysiological approaches at the single-cell level, and toxicological assessment of the novel compounds will be deployed.
Level of originality and innovation: This proposal will enable the first systematic investigation of homoamphetamine derivatives as potential partial releasers at MATs. While alkene hydroaminomethylation already can generate such structures, the expansion of this approach to the incorporation of moieties of ever-increasing complexity promises to make available an entirely new synthetic path to not only homoamphetamines, but aliphatic amines in general. The development of an enantioselective approach, in particular, will constitute a significant innovation in the broad field of amine synthesis.

Link: pharminfo.univie.ac.at/projects/negemac-research-platform/
Duration: 01.05.2022–30.04.2026
Project Partners: Prof. Gerhard Ecker (Faculty of Life Sciences); Prof. Thierry Langer (Faculty of Life Sciences)
Abstract
The NeGeMac research platform addresses several important aspects of the early chemical drug discovery phase:

• data science and deep learning,
• computer‐assisted protein interaction analysis, as well as the
• conformational analysis and prioritization of innovative macrocycles,

which became available recently by applying modern and environmentally efficient organic synthesis methods.

These complementary basic research concepts together provide ‐ as an example, applied to therapeutically interesting protein targets ‐ the basis for the identification of promising starting materials for medicinal chemistry optimization programs. The nationally and internationally well-embedded team put together for this proposal uses this concept to generate potent platform technology that enhances the visibility of the University of Vienna in the area of biopharmaceutical basic research, as well as possibilities for later translational exploitation of the highly effective lead structures that will have been created.