Catalytic Asymmetric [4+2]-Cycloadditions Using Tropolones: Developments, Scope, Transformations, and Bioactivity

Angew Chem Int Ed Engl. 2018 Oct 1;57(40):13216-13220. doi: 10.1002/anie.201808221. Epub 2018 Sep 11.

Abstract

An organocatalyzed asymmetric [4+2]-cycloaddition between tropolones and electron-deficient dienophiles is presented. Complex and biologically interesting dihydrohomobarrelenone scaffolds are formed through a Diels-Alder reaction utilizing bifunctional Brønsted-base catalysis, affording the corresponding bridged bicyclic cycloadducts in up to quantitative yields with good enantio- (up to 92 % ee) and diastereoselectivity (up to >20:1 d.r.). The synthetic value of the obtained products is explored by downstream transformations, including photoisomerizations, and their biological relevancy by in vivo testing in MCF-7 cancer cells.

Keywords: bioactivity; cycloaddition; organocatalysis; photoisomerization; tropolone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Catalysis
  • Cell Survival / drug effects
  • Cycloaddition Reaction
  • Humans
  • MCF-7 Cells
  • Palladium / chemistry
  • Stereoisomerism
  • Tropolone / chemistry*
  • Tropolone / pharmacology

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Palladium
  • Tropolone