This conceptual review examines the ideal multistep synthesis from the perspective of nature. We suggest that besides step- and redox economies, one other key to efficiency is steady state processing with intermediates that are immediately transformed to the next intermediate when formed. We discuss four of nature's strategies (multicatalysis, domino reactions, iteration and compartmentation) that commonly proceed via short-lived intermediates and show that these strategies are also part of the chemist's portfolio. We particularly focus on compartmentation which in nature is found microscopically within cells (organelles) and between cells and on a molecular level on multiprotein scaffolds (e.g. in polyketide synthases) and demonstrate how compartmentation is manifested in modern multistep flow synthesis.
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http://dx.doi.org/10.1039/c4np00160e | DOI Listing |
ACS Meas Sci Au
December 2024
Synthetic Molecule Analytical Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, United States.
Small molecules and antibodies have dominated the pharmaceutical landscape for decades. However, limitations associated with therapeutic targets deemed "undruggable" and progress in biology and chemistry have led to the blossoming of drug modalities and therapeutic approaches. In 2023, a high number of 9 oligonucleotide and peptide products were approved by the Food and Drug Administration (FDA), accounting for 16% of all drugs approved.
View Article and Find Full Text PDFJ Med Internet Res
December 2024
Queensland Digital Health Centre, Centre for Health Services Research, The University of Queensland, Brisbane, Australia.
Traditionally, medical research is based on randomized controlled trials (RCTs) for interventions such as drugs and operative procedures. However, increasingly, there is a need for health research to evolve. RCTs are expensive to run, are generally formulated with a single research question in mind, and analyze a limited dataset for a restricted period.
View Article and Find Full Text PDFNeurotox Res
December 2024
Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, Adeleke University, Ede, Osun State, Nigeria.
Pyrethroids, synthetic insecticides used in pest management, pose health risks, particularly neurotoxic effects, with studies linking exposure to a neurodegenerative disorder. This review examines the neurotoxic mechanisms of pyrethroids analyzing literature from animal model studies. It identifies critical targets for neurotoxicity, including ion channels, oxidative stress, inflammation, neuronal cell loss, and mitochondrial dysfunction.
View Article and Find Full Text PDFAcc Chem Res
December 2024
Max Planck Institute for Marine Microbiology, Celsiusstraße 1, 28359 Bremen, Germany.
Mol Inform
November 2024
Center for Drug Discovery, Faculty of Science, University of Buea, P. O. Box 63, Buea, CM00237, Cameroon.
Diseases caused by viruses are challenging to contain, as their outbreak and spread could be very sudden, compounded by rapid mutations, making the development of drugs and vaccines a continued endeavour that requires fast discovery and preparedness. Targeting viral infections with small molecules remains one of the treatment options to reduce transmission and the disease burden. A lesson learned from the recent coronavirus disease (COVID-19) is to collect ready-to-screen small molecule libraries in preparation for the next viral outbreak, and potentially find a clinical candidate before it becomes a pandemic.
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