Factors to consider for synthesis in 1536-well plates - an amide coupling case study for PROTAC synthesis
Stevens, Rebecca and Palmer, Harry E. P. and Miah, Afjal H. and Burley, Glenn A. (2025) Factors to consider for synthesis in 1536-well plates - an amide coupling case study for PROTAC synthesis. Journal of Organic Chemistry, 90 (6). pp. 2192-2200. ISSN 0022-3263 (https://doi.org/10.1021/acs.joc.4c02456)
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Abstract
Ultra high-throughput chemistry carried out in 1536-well plates is increasingly utilized for reaction optimization protocols and direct-to-biology (D2B) platforms, where nanomolar quantities of the final product are directly assessed for biochemical or cellular activity without purification. As their popularity increases, it is crucial that the synthesis of these molecules is reliable and reproducible. Research in our laboratories has identified several nuances of amide couplings when performed on the nanoscale that result in poor translation from 1536-well plates to batch-scale reactions. This case study presents a nanoscale amide coupling reaction to synthesize 700 PROTAC molecules, which identified a range of factors crucial to reaction success on the nanoscale, despite having no influence on reaction conversion in batch. This work presents a guide for high-throughput chemists to consider when working in 1536-well plates and their importance in drawing conclusions from nanoscale synthesis.
ORCID iDs
Stevens, Rebecca, Palmer, Harry E. P., Miah, Afjal H. and Burley, Glenn A.
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Item type: Article ID code: 91896 Dates: DateEvent14 February 2025Published2 February 2025Published Online21 January 2025AcceptedSubjects: Science > Chemistry > Organic chemistry Department: Faculty of Science > Pure and Applied Chemistry
Technology and Innovation Centre > BionanotechnologyDepositing user: Pure Administrator Date deposited: 28 Jan 2025 13:22 Last modified: 14 Mar 2025 17:35 URI: https://strathprints.strath.ac.uk/id/eprint/91896