ORGANIC
LETTERS
2003
Vol. 5, No. 25
4867-4870
Coumarin-4-ylmethoxycarbonyls as
Phototriggers for Alcohols and Phenols
Akinobu Z. Suzuki, Takayoshi Watanabe, Mika Kawamoto, Keiko Nishiyama,
Hirotaka Yamashita, Megumi Ishii, Michiko Iwamura, and Toshiaki Furuta*
Department of Biomolecular Science, Toho UniVersity, 2-2-1 Miyama,
Funabashi, 274-8510 Japan
Received October 3, 2003
ABSTRACT
Caged compounds can be used to regulate the spatial and temporal dynamics of signaling molecules in live cells. Photochemical properties
of coumarin-4-ylmethoxy carbonates (1a−d) are investigated to construct caged compounds of hydroxy-containing molecules. All the compounds
possess desired properties as phototriggers for alcohols and phenols. The 6-bromo-7-hydroxycoumarin-4-ylmethoxycarbonyl (Bhcmoc) group
has the highest photochemical efficiency and is applied to make caged compounds of 1,2-dioctanoylglycerol (diC ), Tyr-OMe, and adenosine.
8
Caged compounds are synthetic molecules whose biological
activities are masked by covalent attachment of a photo-
chemically removable protecting group (“caging group” or
“phototrigger”) to a functional group, which is of critical
importance to an activity. Intracellular distribution of signal-
ing molecules can be controlled using the chemistry of caged
compounds with high spacial and temporal resolution.1
Coumarin-4-ylmethyls are newly developed phototriggers.
They have higher photolysis efficiencies than others such
as 2-nitrobenzyls, so that the incident light intensity for the
uncaging reaction could be lowered, leading to minimization
of cell damage while maintaining higher spatial resolution.
From recent investigations, the coumarin-type cages, includ-
ing MCM2, HCM (and ACM)3, DMCM,4 BCMCM,5
DMACM (and DEACM),5,6 and Bhc7 have been successfully
applied to protect phosphates,2-7 amines,7a,b,d carboxylates,2b,7
diols,7e and carbonyl compounds.7f Furthermore, the Bhc
group was found to be photolyzed under two-photon excita-
tion conditions with practically useful absorption cross-
sections.7
We investigated photolabile protecting groups for hydroxy
functionality to construct caged compounds of sugars, amino
acids, lipid mediators, and other effector molecules. In a
previous report, we designed and synthesized four arylmethyl
carbonate-type protecting groups, among which the an-
thraquinone-2-ylmethoxycarbonyl (Aqmoc) was found to
offer a unique property as a potential phototrigger for
(5) (a) Hagen, V.; Bendig, J.; Fringe, S.; Eckardt, T.; Helm, S.; Reuter,
D.; Kaupp, U. B. Angew. Chem., Int. Ed. 2001, 40, 1046-1048. (b) Hagen,
V.; Frings, S.; Bendig, J.; Lorenz, D.; Wiesner, B.; Kaupp, U. B. Angew.
Chem., Int. Ed. 2002, 41, 3625-3628.
(6) (a) Geisler, D.; Kresse, W.; Wiesner, B.; Bendig, J.; Kettenmann,
H.; Hagen, V. ChemBioChem 2003, 4, 162-170. (b) Hagen, V.; Frings,
S.; Wiesner, B.; Helm, S.; Kaupp, U. B.; Bendig, J. ChemBioChem 2003,
4, 434-442.
(1) (a) Adams, S. R.; Tsien, R. Y. Annu. ReV. Physiol. 1993, 55, 755-
784. (b) Caged Compounds. In Methods in Enzymology; Marriott, G., Ed.;
Academic Press: New York, 1998; Vol. 291. (c) Curley, K.; Lawrence, D.
S. Pharmacol. Ther. 1999, 82, 347-354. (d) Dorman, G.; Prestwich, G. D.
Trends Biotechnol. 2000, 18, 64-77. (e) Shigeri, Y.; Tatsu, Y.; Yumoto,
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(2) (a) Furuta, T.; Torigai, H.; Sugimoto, M.; Iwamura, M. J. Org. Chem.
1995, 60, 3953-3956. (b) Schade, B.; Hagen, Schmidt, V. R.; Herbrich,
R.; Krause, E.; Eckardt, T.; Bendig, J. J. Org. Chem. 1999, 64, 9109-
9117.
(3) (a) Furuta, T.; Momotake, A.; Sugimoto, M.; Hatayama, M.; Iwamura,
M. Biochem. Biophys. Res. Commun. 1996, 228, 193-198. (b) Furuta, T.;
Iwamura, M. Methods Enzymol. 1998, 291, 50-63.
(4) Eckardt, T.; Hagen, V.; Schade, B.; Schmidt, R.; Schweitzer, C.;
Bendig, J. J. Org. Chem. 2002, 67, 703-710.
(7) (a) Furuta, T.; Wang, S. S.-H.; Dantzker, J. L.; Dore, T. M.; Bybee,
W. J.; Callaway, E. M.; Denk, W.; Tsien, R. Y. Proc. Natl. Acad. Sci.
U.S.A. 1999, 96, 1193-2000. (b) Tsien, R. Y.; Furuta, T. U.S. Patent
Application WO/00/31588, 2000. (c) Ando, H.; Furuta, T.; Tsien, R. Y.;
Okamoto, H. Nat. Genet. 2001, 28, 317-325. (d) Montgomery, H. J.;
Perdicakis, B.; Fishlock, D.; Lajoie, G. A.; Jervis, E.; Guillemette, J. G.
Bioorg. Med. Chem. 2002, 10, 1919-1927. (e) Lin, W.; Lawrence, D. S.
J. Org. Chem. 2002, 67, 2723-2726. (f) Lu, M.; Fedoryak, O. D.; Moister,
B. R.; Dore, T. M. Org. Lett. 2003, 5, 2119-2122.
10.1021/ol0359362 CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/08/2003