Heck diversification of indole‐based substrates under aqueous conditions: from indoles to unprotected halo‐tryptophans and halo‐tryptophans in natural product derivatives

Cristina Pubill-Ulldemolins, Sunil V. Sharma, Chris Cartmell, Jinlian Zhao, Paco Cárdenas, Rebecca J. M. Goss

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
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Abstract

The blending of synthetic chemistry with biosynthetic processes provides a powerful approach to synthesis. Biosynthetic halogenation and synthetic cross‐coupling have great potential to be used together, for small molecule generation, access to natural product analogues and as a tool for chemical biology. However, to enable enhanced generality of this approach, further synthetic tools are needed. Though considerable research has been invested in the diversification of phenylalanine and tyrosine, functionalisation of tryptophans thorough cross‐coupling has been largely neglected. Tryptophan is a key residue in many biologically active natural products and peptides; in proteins it is key to fluorescence and dominates protein folding. To this end, we have explored the Heck cross‐coupling of halo‐indoles and halo‐tryptophans in water, showing broad reaction scope. We have demonstrated the ability to use this methodology in the functionalisation of a brominated antibiotic (bromo‐pacidamycin), as well as a marine sponge metabolite, barettin.
Original languageEnglish
Pages (from-to)10866-10875
Number of pages11
JournalChemistry - A European Journal
Volume25
Issue number46
Early online date19 Jul 2019
DOIs
Publication statusPublished - 14 Aug 2019

Keywords

  • Aqueous cross coupling
  • Barettin
  • Heck reaction
  • Natural product modification
  • Halo-tryptophan

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