An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis

Paul S. Riehl, Jesmine Lim, James D. Finnigan, Simon J. Charnock, Todd K. Hyster

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Herein, we describe a chemoenzymatic synthesis of the bicyclic fragment of Darunavir. A ketoreductase was identified using metagenomic mining to catalyze a highly enantio- and diastereoselective dynamic kinetic resolution of a β-ketolactone. Subsequent lactone reduction with diisobutylaluminum hydride and phase transfer cyclization affords the bicyclic acetal fragment in 39% yield over four steps.

Original languageEnglish (US)
Pages (from-to)2096-2101
Number of pages6
JournalOrganic Process Research and Development
Volume26
Issue number7
DOIs
StatePublished - Jul 15 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Keywords

  • antiviral
  • biocatalysis
  • dynamic kinetic resolution
  • ketoreductase

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