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Grant: Discovery Grants Program - Individual

Queen's University

$103,000.00

New Metal-Catalyzed Reactions for the Synthesis of Bioactive Agents

EF 2024-25

Résumé
Alchemy represents the origin of synthetic chemistry, which envisioned producing valuable and functional products from readily available and inexpensive starting materials. Consequently, the ongoing desire to prepare value-added compounds with unique functionality aided by the development of new spectroscopic techniques to characterize and confirm their identity led to the evolution of the modern chemical and pharmaceutical industries. Nevertheless, despite these enormous advances, the ability to manufacture metric tons of critical materials in a robust and efficient manner remains an ongoing challenge, with an ever-increasing emphasis on the environmental impact of the processes. For example, the challenges associated with developing and manufacturing drugs highlight synthetic chemistry's current strengths and weaknesses. A recent study revealed that the increasing cost of drug discovery, which is ascribed to the low success rate of clinical candidates progressing through the various phases of drug development (0.2%), is attributed to the relatively simple nature of the drugs. The outcome of this inefficient process is that the average cost to market a new drug now exceeds $1.3 billion (CAD) and that only one out of ten drugs generate enough revenue to cover the research and development costs. The study also concludes that more complex structures improve the successful transition from a lead to a commercial entity. Nevertheless, the increased complexity mandates the development of new, more sophisticated synthetic processes to expand the repertoire of methods that can be deployed for their preparation. GOAL: We plan to develop new chemical reactions that facilitate the construction of challenging structural motifs that are not easily accessible by more conventional methods. The proposal will also address the critical and ongoing challenges that limit the scope of the chemistry, which can be ascribed to the lack of insight into the fundamental problem. We have a longstanding program in developing new catalytic reactions using theoretical and mechanistic understanding to provide unique solutions to challenging problems and address important knowledge gaps. We anticipate that this proposal will make significant strides in developing and understanding new methods that facilitate the construction of complex molecules in an efficient, selective and atom-economical manner. IMPACT: The proposal is expected to expand the current "toolkit" of chemical reactions by developing innovative and cutting-edge synthetic methods, thereby providing the HQP with a world-class training environment. The proposed work is highly collaborative, giving the HQP opportunities to work at the interface of chemistry and biology. This unique training environment is expected to enhance Canada's reputation in synthetic organic chemistry by disseminating the work in the form of high-profile publications, news articles and seminars by the HQP.
Programme
Discovery Grants Program - Individual
Bénéficiaire
Emplacement
Ontario, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
NSERC's Awards Data

Tel que publié

Application id
RGPIN-2022-04075
Name nom
Evans, P Andrew
Department département
Chemistry
Organization id
29
Institution établissement
Queen's University
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2024
Competition year année de concours
2022
Award amount
103000
Program id
RGPIN
Program name en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
DISCOVERY RESEARCH
Group fr
RECHERCHE AXÉE SUR LA DÉCOUVERTE
Committee code
1504
Committee name en
Chemistry
Committee name fr
Chimie
Area of application code
1202
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Physical sciences
Area of application fr
Sciences physiques
Research subject code
3704
Research subject group en
Organic chemistry
Research subject group fr
Chimie organique
Research subject en
Synthetic methodology
Research subject fr
Méthodologie en synthèse
Field of research list names en
Not available
Field of research list names fr
Non disponible
Socioeconomic objective list names en
Not available
Socioeconomic objective list names fr
Non disponible
Application title
New Metal-Catalyzed Reactions for the Synthesis of Bioactive Agents
Keywords
carbocyclizations; cross-coupling; dft calculations; dual-catalysis; enantioselective; green chemistry; metal-catalyzed; methodology; multi-component reactions; total synthesis
Application summary
Alchemy represents the origin of synthetic chemistry, which envisioned producing valuable and functional products from readily available and inexpensive starting materials. Consequently, the ongoing desire to prepare value-added compounds with unique functionality aided by the development of new spectroscopic techniques to characterize and confirm their identity led to the evolution of the modern chemical and pharmaceutical industries. Nevertheless, despite these enormous advances, the ability to manufacture metric tons of critical materials in a robust and efficient manner remains an ongoing challenge, with an ever-increasing emphasis on the environmental impact of the processes. For example, the challenges associated with developing and manufacturing drugs highlight synthetic chemistry's current strengths and weaknesses. A recent study revealed that the increasing cost of drug discovery, which is ascribed to the low success rate of clinical candidates progressing through the various phases of drug development (0.2%), is attributed to the relatively simple nature of the drugs. The outcome of this inefficient process is that the average cost to market a new drug now exceeds $1.3 billion (CAD) and that only one out of ten drugs generate enough revenue to cover the research and development costs. The study also concludes that more complex structures improve the successful transition from a lead to a commercial entity. Nevertheless, the increased complexity mandates the development of new, more sophisticated synthetic processes to expand the repertoire of methods that can be deployed for their preparation. GOAL: We plan to develop new chemical reactions that facilitate the construction of challenging structural motifs that are not easily accessible by more conventional methods. The proposal will also address the critical and ongoing challenges that limit the scope of the chemistry, which can be ascribed to the lack of insight into the fundamental problem. We have a longstanding program in developing new catalytic reactions using theoretical and mechanistic understanding to provide unique solutions to challenging problems and address important knowledge gaps. We anticipate that this proposal will make significant strides in developing and understanding new methods that facilitate the construction of complex molecules in an efficient, selective and atom-economical manner. IMPACT: The proposal is expected to expand the current "toolkit" of chemical reactions by developing innovative and cutting-edge synthetic methods, thereby providing the HQP with a world-class training environment. The proposed work is highly collaborative, giving the HQP opportunities to work at the interface of chemistry and biology. This unique training environment is expected to enhance Canada's reputation in synthetic organic chemistry by disseminating the work in the form of high-profile publications, news articles and seminars by the HQP.