Productive Syntheses of Privileged Scaffolds Inspired by the Recognition of a Diels–Alder Pattern Common to Three Classes of Natural Products

Eduard Badarau, K. Harsha Vardhan Reddy, Aurore Loudet, Charles Simon, Laurent Trembleau, Stijn Claerhout, Etienne Pair, Stéphane Massip, Philippe Breton, Brigitte Lesur, Solo Goldstein, Jean Marie Fourquez, Jean Michel Henlin, Léon Ghosez*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Identification of a common Diels–Alder pattern in three classes of bioactive natural products led us to study the synthesis and cycloaddition of a new class of cyclic dienes readily available from β,γ-unsaturated lactams. A practical and readily scalable route to the parent p-methoxybenzyl-protected 6- and 7-membered β,γ-unsaturated lactams was developed. These were readily transformed into the corresponding O-silylated dienes, which were reacted with dimethyl and diethyl fumarate to yield stereoselectively highly functionalized bicyclic adducts. These exhibited unexpected and versatile transformations upon acid hydrolysis depending on the nature of the dienophile substituents and the acid catalyst. All reactions have been performed on multigram quantities. These transformations provide a convenient, economical, and easily scalable pathway for the rapid construction of functionally and stereochemically dense privileged scaffolds for the construction of libraries of natural products-inspired molecules of pharmacological relevance.

Original languageEnglish
Number of pages6
JournalChemistry - A European Journal
Volume26
Early online date19 May 2020
DOIs
Publication statusPublished - 17 Sep 2020

Keywords

  • cycloaddition
  • lactams
  • molecular diversity
  • natural products
  • pattern recognition
  • GUIDING PRINCIPLES
  • COMPLEX
  • DRUG DISCOVERY
  • BETA-AZIDO FUNCTIONALIZATION
  • DIVERSITY-ORIENTED SYNTHESIS
  • RING-CLOSING METATHESIS
  • HETEROCYCLES
  • CYCLOADDITIONS
  • ENOL ETHER CHEMISTRY
  • CHEMICAL SPACE

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