Synthesis of Isotopically Labeled Anti-HIV Nucleoside Islatravir through a One-Pot Biocatalytic Cascade Reaction
Sumei Ren, Mark A. Huffman, Aaron M. Whittaker, Hao Yang, Christopher C. Nawrat, David J. Waterhouse, Kevin M. Maloney, Neil A. Strotman
Abstract
We report the synthesis of the carbon-14-labeled unnatural nucleoside islatravir, an investigational HIV drug, through a one-pot biocatalytic cascade starting from acetaldehyde-2-14C. Combining enzymatic reactions into multistep biocatalytic cascades accelerates delivery and increases the yield, and in this synthesis it has the added benefits of eliminating handling of radioactive intermediates and minimizing radioactive waste.
Topics & Concepts
ChemistryYield (engineering)Cascade reactionCascadeCombinatorial chemistryAcetaldehydeBiocatalysisHuman immunodeficiency virus (HIV)NucleosideOrganic chemistryCatalysisStereochemistryReaction mechanismEthanolChromatographyMaterials scienceVirologyMetallurgyBiologyChemical Reactions and IsotopesAmino Acid Enzymes and MetabolismBiochemical and Molecular Research