Total Synthesis of Darobactin A

J Am Chem Soc. 2022 Aug 10;144(31):14026-14030. doi: 10.1021/jacs.2c05891. Epub 2022 Jul 28.

Abstract

The collaborative total synthesis of darobactin A, a recently isolated antibiotic that selectively targets Gram-negative bacteria, has been accomplished in a convergent fashion with a longest linear sequence of 16 steps from d-Garner's aldehyde and l-serine. Scalable routes toward three non-canonical amino acids were developed to enable the synthesis. The closure of the bismacrocycle was realized through sequential, halogen-selective Larock indole syntheses, where the proper order of cyclizations proved crucial for the formation of the desired atropisomer of the natural product.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehydes* / chemistry
  • Amino Acids* / chemistry
  • Cyclization
  • Phenylpropionates
  • Stereoisomerism

Substances

  • Aldehydes
  • Amino Acids
  • Phenylpropionates
  • darobactin