Synthesis of hexahydropyrrolo[2,1-a]isoquinoline compound libraries through a Pictet–Spengler cyclization/metal-catalyzed cross coupling/amidation sequence

Rico Petersen, A. Emil Cohrt, Michael Åxman Petersen, Peng Wu, Mads Hartvig Clausen, Thomas Eiland Nielsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Molecular libraries of natural product-like and structurally diverse compounds are attractive in early drug discovery campaigns. In here, we present synthetic methodology for library production of hexahydropyrrolo[2,1-a]isoquinoline (HPIQ) compounds. Two advanced HPIQ intermediates, both incorporating two handles for diversification, were synthesized through an oxidative cleavage/Pictet–Spengler reaction sequence in high overall yields. A subsequent metal-catalyzed cross coupling/amidation protocol was developed and its utility in library synthesis was validated by construction of a 20-membered natural product-like molecular library in good overall yields.
Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Volume23
Issue number11
Pages (from-to)2646-2649
Number of pages4
ISSN0968-0896
DOIs
Publication statusPublished - 2015

Keywords

  • Drug discovery
  • Molecular libraries
  • Heterocycles
  • Pictet–Spengler
  • Molecular diversity

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