Nine-Step Stereoselective Synthesis of Islatravir from Deoxyribose
Christopher C Nawrat1, Aaron M Whittaker1, Mark A Huffman1
1Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
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.
Related Concept Videos
Preparation of Diols and Pinacol Rearrangement
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
[3,3] Sigmatropic Rearrangement of Allyl Vinyl Ethers: Claisen Rearrangement
Preparation of Alcohols via Substitution Reactions
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction


