Nine-Step Stereoselective Synthesis of Islatravir from Deoxyribose.


Journal

Organic letters
ISSN: 1523-7052
Titre abrégé: Org Lett
Pays: United States
ID NLM: 100890393

Informations de publication

Date de publication:
20 03 2020
Historique:
pubmed: 29 2 2020
medline: 11 6 2021
entrez: 29 2 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32108487
doi: 10.1021/acs.orglett.0c00239
doi:

Substances chimiques

Alkynes 0
Deoxyadenosines 0
Reverse Transcriptase Inhibitors 0
Silanes 0
Deoxyribose 533-67-5
islatravir QPQ082R25D

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2167-2172

Auteurs

Christopher C Nawrat (CC)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Aaron M Whittaker (AM)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Mark A Huffman (MA)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Mark McLaughlin (M)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Ryan D Cohen (RD)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Teresa Andreani (T)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Bangwei Ding (B)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Hongming Li (H)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Mark Weisel (M)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

David M Tschaen (DM)

Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

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Classifications MeSH