Table 2 CuAAC of various 2-5A analogues with 4-fluorobenzylazidea
bearing 5-ethynyl-1,3-benzenedimethanol rapidly reacted with
benzylazide compounds to produce the cycloaddition products
in good to excellent yield. To the best of our knowledge, this is
the first reported method for PET labelling of RNA oligomers.
This work was supported by the Molecular Imaging
Research Program and Grants-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and
Technology (MEXT) of Japan.
13
(equiv.) Product
Yieldb
(%)
Entry Substrate
Notes and references
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1
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42
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2
3
5
99
99
0.2
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a
Reaction conditions: CuSO4ꢁ5H2O (100 equiv.), sodium ascorbate
(100 equiv.), 0.1 M phosphate buffer (pH 7.0)/DMSO/MeCN =
b
134 : 20 : 22. The yield was determined based on the HPLC analysis.
Fig. 1 Sequences of miRNA-143 analogues.
We have also studied the role of anti-oncomirs miRNA-143
in human colorectal tumors.21 To investigate the generality of
the present method, we synthesised short single-strand RNAs
18 and 19 bearing 1 at the 30-end. Both 18 and 19 include a
sequence of miRNA-143 (Fig. 1).
In both cases, the coupling reactions with 4-fluorobenzyl-
azide (13) (10.0 equiv.) were completed within 15 min and
provided the cycloaddition products 20 and 21 in good yields
(Table 3).
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Bioorg. Med. Chem. Lett., 1992, 2, 1623–1626.
In conclusion, we have developed aryl acetylene derivatives
and a rapid ligand-free copper-catalyzed azide–alkyne cyclo-
addition for PET labelling of RNA oligomers. RNA oligomers
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K. T. Nakamura, EMBO J., 2004, 23, 3929–3938.
13 M. Nakanishi, N. Tanaka, Y. Mizutani, M. Mochizuki, Y. Ueno,
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Table 3 CuAAC of miRNA-143 analogues with 4-fluorobenzylazidea
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Entry
miRNA-143 analogue
Product
Yieldb (%)
1
2
18
19
20
21
83
82
a
Reaction conditions: 4-fluorobenzylazide (10 equiv.), CuSO4ꢁ5H2O
(100 equiv.), sodium ascorbate (100 equiv.), 0.1 M phosphate buffer
b
(pH 7.0)/DMSO/MeCN = 134 : 20 : 22. The yield was determined
based on the HPLC analysis.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 2691–2693 2693