title: Exploration of the labeling of [11C]tubastatin A at the hydroxamic acid site with [11C]carbon monoxide.
abstract: We aimed to label tubastatin A (1) with carbon-11 (t1/2 = 20.4 min) in the hydroxamic acid site to provide a potential radiotracer for imaging histone deacetylase 6 in vivo with positron emission tomography. Initial attempts at a one-pot Pd-mediated insertion of [(11)C]carbon monoxide between the aryl iodide (2) and hydroxylamine gave low radiochemical yields (<5%) of [(11) C]1. Labeling was achieved in useful radiochemical yields (16.1 ± 5.6%, n = 4) through a two-step process based on Pd-mediated insertion of [(11)C]carbon monoxide between the aryl iodide (2) and p-nitrophenol to give the [(11)C]p-nitrophenyl ester ([(11)C]5), followed by ultrasound-assisted hydroxyaminolysis of the activated ester with excess hydroxylamine in a DMSO/THF mixture in the presence of a strong phosphazene base P1-t-Bu. However, success in labeling the hydroxamic acid group of [(11)C]tubastatin A was not transferable to the labeling of three other model hydroxamic acids.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Shuiyu
authors.initials: S
authors.lastname: Lu
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Kalin
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kozikowski
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
mesh_terms: D002248:Carbon Monoxide / Q000737:chemistry*; D002250:Carbon Radioisotopes / Q000737:chemistry; D006877:Hydroxamic Acids / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
chemical_list: D002250:Carbon Radioisotopes; D006877:Hydroxamic Acids; D007211:Indoles; D019275:Radiopharmaceuticals; C553587:tubastatin A; D002248:Carbon Monoxide
keywords: Carbonylation; HDAC6; Hydroxyaminolysis; [11C]Carbon monoxide; [11C]tubastatin A