Tetrahedron Letters
Fluorogenic probes for chemical transformations: 9-anthracene
derivatives for monitoring reaction progress by an increase in
fluorescence
b
c,d,
Nobuyuki Mase a,b, , Kunihiko Takabe , Fujie Tanaka
⇑
⇑
a Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, and Green Energy Research Division, Research Institute of Green Science and Technology,
Shizuoka University, 3-5-1 Johoku, Hamamatsu, Shizuoka 432-8561, Japan
b Department of Molecular Science, Faculty of Engineering, Shizuoka University, 3-5-1 Johoku, Hamamatsu, Shizuoka 432-8561, Japan
c Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan
d Okinawa Institute of Science and Technology Graduate University, Mikuruma, 448-5 Kajii, Kamigyo, Kyoto 602-0841, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The development of fluorogenic probes for chemical transformations bearing anthracene as a fluorescent
core moiety is reported. Fluorogenic probes were designed by linking anthracene with functional groups
used for reactions of interest. Each fluorogenic probe, possessing a reaction group such as aldehyde, a,b-
unsaturated ketone, or imine at the 9-position of the anthracene, showed no or very low fluorescence.
Reaction products of the probes, including aldol and addition products, were highly fluorescent. The
products showed more than 1000-fold higher fluorescence than did the fluorogenic probes under the
same conditions. The utility of the fluorogenic probes was demonstrated in monitoring the progress of
a catalyzed aldol reaction.
Received 2 May 2013
Revised 29 May 2013
Accepted 4 June 2013
Available online 10 June 2013
Keywords:
Fluorogenic probe
Fluorescent molecules
High-throughput screening
Carbon–carbon bond formation
Reaction sensor
Ó 2013 Elsevier Ltd. All rights reserved.
Fluorogenic substrates or probes for chemical transformations,
molecules that show no or very low fluorescence but show high
fluorescence upon chemical transformations, are useful for moni-
toring the progress of chemical transformations.1–5 Analyses of
the fluorescence increase correlated to the product formation un-
der no or very weak fluorescence conditions are highly sensitive
to detect the formation of low concentrations of the product, com-
pared to the analysis of the fluorescence decrease related to the
consumption of fluorescent substrates.1,3e Thus, when a fluoro-
genic probe is used in a reaction, formation of the fluorescent prod-
uct can be evaluated at initial stages of the reaction.1–3 Assays
using fluorogenic substrates accelerate rapid identification of supe-
rior catalysts and reaction conditions in high-throughput formats
as well as characterization of catalysis on a small scale. Here, we
report the development of 9-anthracene-derived fluorogenic
probes (Fig. 1) and their use in monitoring various chemical trans-
formations, including C–C bond-forming reactions.
when the amino group is not protonated; upon protonation, the
compounds become highly fluorescent.7 Because aldehydes conju-
gated with aryl groups and
a,b-unsaturated compounds often
quench fluorescence,2,3 we reasoned that anthracene with one of
these functional groups should be a candidate for fluorogenic sub-
strates. When the reacting functional group of the fluorogenic sub-
strate candidate is transformed to a non-quenching group, an
increase in fluorescence will be observed as the reaction progresses.
We reasoned that by linking a highly fluorescent anthracene moiety
to reacting functional groups that quench the anthracene fluores-
cence, fluorogenic probes with great fluorogenic ranges for chemical
transformations would be generated. Note that although many fluo-
rescence-based sensors derived from 9-anthracene have been
developed for detecting certain molecules through noncovalent
binding and changes in protonated stages,8 no examples of anthra-
cene-based fluorogenic probes have been reported to detect cova-
lent bond-formations and other chemical transformations.
Many 9-anthracene derivatives are highly fluorescent; however,
the fluorescence depends on the substituents.6 For example, ami-
nomethylanthracenes are weakly fluorescent or non-fluorescent
O
O
S
O
O
Ph
N
Ar =
H
Ar
Ar
H
Ar
⇑
Corresponding authors. Tel./fax: +81 53 478 1196 (N.M.); tel.: +81 75 741 6864;
fax: +81 75 741 6865 (F.T.).
1
2
3
Tanaka).
Figure 1. Fluorogenic substrate probes developed in this study.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.