A groundbreaking approach was the development of a novel monomethylated pyrroliquinoline derivative by a team of researchers from the School of Human Sciences, Metropolitan University, London. The team led by Dr. Bhaven Patel also includes Margarita Damai, Dr. Norman Guzzardi, Dr. Viliyana Lewis, Dr. Zenobia Rao and Dr. Daniel Sykes. Their innovative approach uses shared precursors and has been successfully applied to the full synthesis of Marinoquinoline A. The results of the study were published in the peer-reviewed journal RSC Advanceds.
Nitrogen-containing heterocycles are crucial in natural products and medicinal chemistry and provide important biological activities. Traditionally, the synthesis of pyrroliquinoline is faced with challenges due to toxic and dangerous methods. The new strategy described by Dr. Patel and his team involves the addition of unstable methyl radicals to the aryl isocyanide under specific reaction conditions, resulting in monomethylated derivatives. “This novel approach not only simplifies the synthesis process, but also improves the safety and efficiency of producing these biologically active compounds,” explains Dr. Patel.
The researchers focused on optimizing the conditions for selective methylation. They found that the use of bisamino oxidized diamino (DCP) as the source of methyl radicals provides the highest yields for monomethylated products. However, when Fenton reaction conditions are applied, the bimethylated pyrroliquinoline is mainly formed. Selective control of the methylation process is a major advance in this field.
The key to this study is the successful application of this method in the total synthesis of Marinoquinoline A, a natural product known for its acetylcholinesterase inhibitory properties. “Our method allows us to effectively synthesize manoquinoline A in just five steps from the commercially available starting materials.” This achievement underscores the practicality of their approach in producing complex natural products,” Dr. Patel noted. Practicality.
Given their various biological activities, including anti-cancer, antimalarial and anti-proliferative effects, the team’s findings demonstrate the potential of these novel derivatives in these novel medicinal chemistry. “The magic methyl effect, the addition of methyl can significantly increase the binding affinity and efficacy of the drug, which emphasizes the importance of our work,” Dr. Patel said.
Patel and colleagues detailed the synthesis process in their study, starting with the preparation of cyclic precursors. They used various methods to produce methyl radicals and eventually found that DCP provided the best results. The team also explored the electron effects of different cyclization precursors, with most isocyanides successfully circulating except for electron-rich variants.
This study not only promotes the synthesis of pyrroliquinoline derivatives, but also develops new avenues for the development of nitrogen-based heterocycles with important pharmaceutical applications. “Our approach provides a versatile, effective pathway to the versatile pathway of synthetic bioactive compounds, paving the way for future paths discovered in drug development,” Dr. Patel stressed.
Margarita Damai’s contribution to the study resulted in the 700 nominated RSC Distinguished Student Paper Award in the Organic Chemistry category.
Journal Reference
Margarita damai, Norman Guzzardi, Viliyana Lewis, Zenobia X. Rao, Daniel Sykes and Bhaven Patel. “Making single and novel bimethylated pyrrolidinate derivatives from common precursors and their application in the total synthesis of Marinoquinoline A.” RSC Advanceds (2023). doi: https://doi.org/10.1039/d3ra05952a
About the Author
Bhaven Patel is a reader of Organic Chemistry at Metropolitan University in London. He received his PhD in Chemistry MSCI and Organic Chemistry from King’s College London and the University of Birmingham. He then received the prestigious EPSRC PhD Plus scholarship and worked at the University of Birmingham and Queensland Technical University. He has also worked as a postdoctoral fellow at the University of Nottingham and UCL School of Pharmacy. He is currently co-chair of the topic of applied chemistry and drug technology research and is a fellow of the Royal Chemistry Society. His current scientific interests merge reaction discoveries, namely the development of innovative synthetic methods, including in the synthesis of natural products and the application of bioactive molecules. His expertise also extends to the application of medicinal chemistry and 3D printing in science. Recently, his research has focused on the development of new chemical sensors.
Daniel Sykes Received a year in the industry from the University of Manchester and received MCHEM (Honors). He stayed in Manchester to study for his PhD under the supervision of Professor Stephen Faulkner. After working at the University of Manchester, Oxford and Sheffield, he moved to the Metropolitan University of London and is now the head of Chemistry and Pharmacy Sciences. He is a member of the Royal Chemistry Society and his research has been cited more than 1,000 times. His research interests include photophysical measurements of metal complexes, especially iris and F-block metals, focusing on the energy transfer process between them. This work has recently expanded to cell imaging and uses the complex as a launch probe for diagnostic applications.
Margarita Damai He is a second-year student at Metropolitan University in London, pursuing a BSC biomedical degree. Her research work mainly revolves around the synthesis of complex molecular structures and their application in medicinal chemistry. She is an active person and has attended several research meetings to represent her work. In addition to research, margarita was involved in democracy, especially within the London Met Student Union, where she served on a year off.
