Document Type
Article
Publication Date
2026
Publication Title
ACS Omega
Keywords
anions, inhibitors, mixtures, organochlorine, peptides and proteins
Abstract
An asymmetric glycolate aldol addition pathway was developed for the synthetic preparation of a series of protease inhibitors based on the hydroxyethylamine structural motif. A single glycolate aldol adduct derived from a highly diastereoselective (≥95:5 d.r.) asymmetric aldol reaction served as the starting point for the synthesis of the inhibitors. The starting material is easily prepared and purified via recrystallization on multigram scales. This work describes the synthesis of the HIV protease inhibitor TMC-126, the Plasmepsin X (PMX) inhibitor 49c for the treatment of malaria, and a computationally derived inhibitor for the 3CLpro of the SARS-CoV-2 from a single common synthetic intermediate.
Funding Source
The authors thank the Department of Chemistry at Illinois State University for material support. This article was published Open Access thanks to a transformative agreement between Milner Library and ACS.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
DOI
10.1021/acsomega.6c01499
Recommended Citation
Affram, K. A., Carter, A., Breede, A., Kimsey, A., Hemeson, G., Semakieh, B., Martinez, M., Ayim, E., Odeh, J., & Hitchcock, S. R. (2026). Asymmetric Synthesis of the HIV Protease Inhibitor TMC-126, a PMX Antimalarial Protease Inhibitor, and a Putative COVID-19 Inhibitor Using a Highly Stereoselective Glycolate Aldol Addition Reaction Pathway. ACS Omega. https://doi.org/10.1021/acsomega.6c01499
Comments
First published in ACS Omega (2026): https://doi.org/10.1021/acsomega.6c01499