Nine-Step Stereoselective Synthesis of Islatravir from Deoxyribose
Christopher C. Nawrat, Aaron M. Whittaker, Mark A. Huffman, Mark McLaughlin, Ryan D. Cohen, Teresa Andreani, Bangwei Ding, Hongming Li, Mark Weisel, David M. Tschaen
Abstract
A stereoselective nine-step synthesis of the potent HIV nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir (EfdA, MK-8591) from 2-deoxyribose is described. Key findings include a diastereodivergent addition of an acetylide nucleophile to an enolizable ketone, a chemoselective ozonolysis of a terminal olefin and a biocatalytic glycosylation cascade that uses a unique strategy of byproduct precipitation to drive an otherwise-reversible transformation forward.
Topics & Concepts
ChemistryStereoselectivityDeoxyriboseStereochemistryGlycosylationAcetylideOlefin fiberOzonolysisCombinatorial chemistryDihydroxylationNucleophileNucleic acidOrganic chemistryEnantioselective synthesisBiochemistryCatalysisPolymerHIV/AIDS drug development and treatmentBiochemical and Molecular ResearchCarbohydrate Chemistry and Synthesis