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Heck Diversification of Indole‐Based Substrates under Aqueous Conditions: From Indoles to Unprotected Halo‐tryptophans and Halo‐tryptophans in Natural Product Derivatives
Author(s) -
PubillUlldemolins Cristina,
Sharma Sunil V.,
Cartmell Christopher,
Zhao Jinlian,
Cárdenas Paco,
Goss Rebecca J. M.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201901327
Subject(s) - natural product , tryptophan , indole test , chemistry , combinatorial chemistry , stereochemistry , biochemistry , amino acid
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.