Exploration of the labeling of [11C]tubastatin A at the hydroxamic acid site with [11C]carbon monoxide

Shuiyu Lu, Yi Zhang, Jay H. Kalin, Lisheng Cai, Alan P. Kozikowski, Victor W. Pike

Research output: Contribution to journalArticle

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 [11C]carbon monoxide between the aryl iodide (2) and hydroxylamine gave low radiochemical yields (<5%) of [11C]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 [11C]carbon monoxide between the aryl iodide (2) and p-nitrophenol to give the [11C]p-nitrophenyl ester ([11C]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 [11C]tubastatin A was not transferable to the labeling of three other model hydroxamic acids.

Original languageEnglish (US)
Pages (from-to)9-13
Number of pages5
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Carbonylation
  • HDAC6
  • Hydroxyaminolysis
  • [C]Carbon monoxide
  • [C]tubastatin A

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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