Biomimetic synthesis of the IDO inhibitors exiguamine A and B

Matthew Volgraf; Jean-Philip Lumb; Harry C Brastianos; Gavin Carr; Marco K W Chung; Martin Münzel; A Grant Mauk; Raymond J Andersen; Dirk Trauner

doi:10.1038/nchembio.107

Biomimetic synthesis of the IDO inhibitors exiguamine A and B

Nat Chem Biol. 2008 Sep;4(9):535-7. doi: 10.1038/nchembio.107.

Authors

Matthew Volgraf¹, Jean-Philip Lumb, Harry C Brastianos, Gavin Carr, Marco K W Chung, Martin Münzel, A Grant Mauk, Raymond J Andersen, Dirk Trauner

Affiliation

¹ Department of Chemistry, University of California, Berkeley, California 94720, USA.

PMID: 18677305
DOI: 10.1038/nchembio.107

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomimetic Materials / chemical synthesis*
Biomimetic Materials / chemistry
Catecholamines* / biosynthesis
Catecholamines* / chemical synthesis
Catecholamines* / chemistry
Cyclization
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Indole Alkaloids / chemical synthesis*
Indole Alkaloids / chemistry
Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
Indoles / chemical synthesis*
Indoles / chemistry
Molecular Structure
Oxidation-Reduction
Quinones / chemical synthesis*
Quinones / chemistry
Spiro Compounds / chemical synthesis*
Spiro Compounds / chemistry

Substances

Catecholamines
Enzyme Inhibitors
Indole Alkaloids
Indoleamine-Pyrrole 2,3,-Dioxygenase
Indoles
Quinones
Spiro Compounds
exiguamine A
exiguamine B