Abstract
Biomimetic synthesis is an attempt to assemble natural products along biosynthetic lines without recourse to the full enzymatic machinery of nature. We exemplify this with a total synthesis of exiguamine A and the newly isolated natural product exiguamine B. The most noteworthy feature of this work is an oxidative endgame drawing from the complex chemistry of catecholamines, which allows for ready access to a new class of nanomolar indoleamine-2,3-dioxygenase inhibitors.
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Acknowledgements
Financial support at University of California Berkeley was provided by Novartis (D.T.), Roche Pharmaceuticals (D.T., M.V.), Wyeth Research (M.V.), the American Chemical Society (ACS) Medicinal Chemistry Division (M.V.), Pfizer, Inc. (J.-P.L.) and the ACS Organic Division (J.-P.L.) in the form of predoctoral fellowships and a Young Investigator Award. Financial support at University of British Columbia was provided by the National Cancer Institute of Canada (NCIC) and the Canadian Cancer Society (CCS) (R.J.A.), the National Science and Engineering Research Council of Canada (R.J.A.), NCIC and CCS (A.G.M.), the Michael Smith Foundation for Health Research (Grant INUFB074031) and a Canada Research Chair (A.G.M.).
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Volgraf, M., Lumb, JP., Brastianos, H. et al. Biomimetic synthesis of the IDO inhibitors exiguamine A and B. Nat Chem Biol 4, 535–537 (2008). https://doi.org/10.1038/nchembio.107
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DOI: https://doi.org/10.1038/nchembio.107
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