Flexible and Convergent Enantioselective Total Synthesis of (R)-Juglanaloids A and B: Two Phthalide Spiro Alkaloids with Potential Alzheimer's Disease Inhibitory Activity

J Org Chem. 2024 May 17;89(10):7255-7262. doi: 10.1021/acs.joc.4c00740. Epub 2024 May 8.

Abstract

Juglanaloids A and B are recently isolated natural products characterized by an unprecedented spiro bicyclic isobenzofuranone-tetrahydrobenzazepinone framework and a promising antiamyloid activity. Here reported is a straightforward convergent total synthesis of these natural products, which were obtained in high enantiomeric purity (94% and >99% ee for juglanaloids A and B, respectively) through an eight-step longest linear sequence, based on an efficient and reliable enantioselective phase-transfer-catalyzed alkylation step. Considering the interesting biological activity of juglanaloids, this convenient, highly enantioselective, flexible, and predictable synthetic strategy promises to be a powerful tool for accessing potentially bioactive spiro bicyclic phthalide-tetrahydrobenzazepinone derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids* / chemical synthesis
  • Alkaloids* / chemistry
  • Alkaloids* / pharmacology
  • Alzheimer Disease* / drug therapy
  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry
  • Benzofurans / pharmacology
  • Molecular Structure
  • Spiro Compounds* / chemical synthesis
  • Spiro Compounds* / chemistry
  • Spiro Compounds* / pharmacology
  • Stereoisomerism

Substances

  • phthalide