Total Synthesis of (+)-Brevianamides A and B

Org Lett. 2024 Dec 13;26(49):10424-10429. doi: 10.1021/acs.orglett.4c03026. Epub 2024 Oct 10.

Abstract

(+)-Brevianamides A (1a) and B (1b) are distinguished by their unique bicyclo[2.2.2]diazaoctane structure and have captured the interest of synthetic chemists due to their fascinating array of biological activities. The biosynthetic proposal of these classes of alkaloids led to the discovery of a number of interesting strategies. We present a biomimetic synthesis of these alkaloids starting from naturally occurring 4-hydroxy-l-proline and L-tryptophan. Gratifyingly, we emulate an alternative biosynthetic process through a unique elimination-isomerization sequence triggered by a dual-base system to generate the key aza-diene required for the Diels-Alder reaction to craft the bicyclo[2.2.2]diazaoctane structure.

MeSH terms

  • Alkaloids* / chemical synthesis
  • Alkaloids* / chemistry
  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / chemistry
  • Cycloaddition Reaction
  • Molecular Structure
  • Piperazines* / chemical synthesis
  • Piperazines* / chemistry
  • Proline / chemistry
  • Spiro Compounds* / chemical synthesis
  • Spiro Compounds* / chemistry
  • Stereoisomerism
  • Tryptophan / analogs & derivatives
  • Tryptophan / chemical synthesis
  • Tryptophan / chemistry

Substances

  • Alkaloids
  • Bridged Bicyclo Compounds
  • Proline
  • Tryptophan
  • brevianamide A
  • brevianamide B
  • Piperazines
  • Spiro Compounds