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Exploration of the labeling of [ 11 C]tubastatin A at the hydroxamic acid site with [ 11 C]carbon monoxide
Author(s) -
Lu Shuiyu,
Zhang Yi,
Kalin Jay H.,
Cai Lisheng,
Kozikowski Alan P.,
Pike Victor W.
Publication year - 2016
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3360
Subject(s) - chemistry , hydroxamic acid , carbon monoxide , hydroxylamine , aryl , iodide , medicinal chemistry , stereochemistry , organic chemistry , catalysis , alkyl
We aimed to label tubastatin A (1) with carbon‐11 ( t 1/2 = 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 P 1 ‐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.