Heck diversification of indole‐based substrates under aqueous conditions : from indoles to unprotected halo‐tryptophans and halo‐tryptophans in natural product derivatives
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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.
Pubill-Ulldemolins , C , Sharma , S V , Cartmell , C , Zhao , J , Cárdenas , P & Goss , R J M 2019 , ' Heck diversification of indole‐based substrates under aqueous conditions : from indoles to unprotected halo‐tryptophans and halo‐tryptophans in natural product derivatives ' , Chemistry - A European Journal , vol. 25 , no. 46 , pp. 10866-10875 . https://doi.org/10.1002/chem.201901327
Chemistry - A European Journal
2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DescriptionThe research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013/ERC grant agreement no 614779 GenoChemetics (to R.J.M.G). P. C. is supported by the European Union's Horizon 2020 research and innovation program through the SponGES project (grant agreement No. 679849). C.P-U. was supported by the Marie Sklodowska-Curie Fellowship C-XAq.
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