Biomimetic total syntheses of borreverine and flinderole alkaloids

J Org Chem. 2013 Oct 18;78(20):10106-20. doi: 10.1021/jo4013833. Epub 2013 Oct 1.

Abstract

Dimeric indole alkaloids represent a structurally unique class of natural products having interesting biological activities. Recently, we reported the first total synthesis of flinderoles B and C, structurally unique and potent antimalarial natural products. Central to the design of the approach and by virtue of a one-pot, acid-catalyzed dimerization reaction, the route also provided total synthesis of the borreverine class of natural products. This full account details the progress of efforts that culminated in the protecting-group-free, six-step total synthesis of all of the flindersia alkaloids: dimethylisoborreverine, isoborreverine, flinderoles A-C, and their analogues. A biomimetic approach featuring a scalable and catalytic formal [3 + 2] cycloaddition and Diels-Alder reaction is outlined in detail. On the basis of the experimental observations, a detailed mechanism has been proposed for the dimerization of tertiary alcohol 28.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Biological Products
  • Biomimetics
  • Cycloaddition Reaction
  • Dimerization
  • Indole Alkaloids / chemical synthesis*
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / pharmacology
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Stereoisomerism

Substances

  • Alkaloids
  • Antimalarials
  • Biological Products
  • Indole Alkaloids
  • Indoles
  • flinderole B
  • flinderole C
  • borreverine