Synthesis and stereochemical assignment of brasilibactin A.
[structure: see text] Brasilibactin A, a naturally occurring siderophore related to the mycobactins, has been synthesized in six steps. Use of asymmetric titanium-mediated aldol reactions allowed the preparation of both diastereomers from a common synthetic intermediate, thus allowing the relative stereochemistry of the natural product to be assigned. Brasilibactin A exhibits no inhibition of histone deacetylases (HDACs) in spite of the N-formyl-N-hydroxy lysine moiety that is expected to affect the activity of these metal-dependent lysine-modifying enzymes.
Mitchell
Judith M
JM
Broad Institute of Harvard and MIT Chemical Biology Program, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Shaw
Jared T
JT
D000577:Amides / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D006900:Hydroxylation; D008239:Lysine / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry; D013229:Stearic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D053778:Thiazolidines / Q000737:chemistry
D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D008670:Metals; D010080:Oxazoles; D013229:Stearic Acids; D053778:Thiazolidines; C499911:brasilibactin A; C018608:mycobactins; C033089:thiazoline-2-thione; D006655:Histone Deacetylases; D008239:Lysine