3716
R. Ziessel et al. / Tetrahedron Letters 53 (2012) 3713–3716
position of the resulting compounds is likely due to the presence of
the electron-rich triple bond.
through a grant for Specific Targeted Research Project (POC4Life-
LSHB-CT-2007-037933). Professor Jack Harrowfield (ISIS in Stras-
bourg) is warmly acknowledged for critical reading of this manu-
script prior to publication and for providing key references to
this contribution.
The most efficient pathway to a pyridine-based ligand carrying
an ionizable phosphonic acid group was that of the substitution
reaction with the deprotected reagent CH. The use of dried basic
alumina as the interface enabled the preparation of ligand 13 in
modest yields. The ligand was isolated pure, after removal of the
alumina by filtration and precipitation of the compound with
diethylether after acidification (Scheme 3).
Additional functionalization of the frameworks is feasible using
palladium catalysis to introduce flexible side chains carrying ter-
minal carboxylic acids. These are important substituents for Schot-
ten–Bauman linking of the probes to biological material or
heterogeneous surfaces, as we have previously demonstrated. As
shown in Scheme 4, the naphthalene-bromo function was easily
cross-linked to ethyl 6-heptynoate, affording the highly functional-
ized derivatives 15 and 17 in excellent yields (72–78%), or to ethyl
4-aminobutanoate under a flux of CO at atmospheric pressure,
leading to compounds 14 and 16 in good yields (64–74%). Simulta-
neous hydrolysis of the carboxylic ester side-chain as well as the
phosphonate and the carboxylic ester of the complexation pocket
was conveniently achieved using appropriate amounts of NaOH
in THF/water mixtures.
References and notes
1. (a) Brunet, E.; Juanes, O.; Rodriguez-Ubis, J. C. Curr. Chem. Biol. 2007, 1, 11–39;
(b) Eliseeva, S. V.; Bünzli, J. C. G. Chem. Soc. Rev. 2010, 39, 189–227.
2. (a) Constable, E. C. Chem. Soc. Rev. 2007, 36, 246–253; (b) Heller, M.; Schubert,
U. S. Eur. J. Org. Chem. 2003, 947–961; (c) Halcrow, M. A. Coord. Chem. Rev. 2005,
249, 2880–2908.
3. Bünzli, J.-C. G. Chem. Rev. 2010, 110, 2729–2755.
4. (a) Bünzli, J.-C. G.; Piguet, C. Chem. Soc. Rev. 2005, 34, 1048–1077; (b) Comby S.,
Bünzli, J.-C. G., Handbook on the Physics and Chemistry of Rare Earths, Vol. 37,
edited by K.A. Gschneidner, Jr., J.-C.G. Bünzli and V.K. Pecharsky.
5. Sabbatini, N.; Guardigli, M.; Lehn, J.-M. Coord. Chem. Rev. 1993, 123, 201–228.
6. (a) Alpha, B.; Lehn, J.-M.; Mathis, G. Angew. Chem., Int. Ed. 1987, 26, 266–267;
(b) Alpha, B.; Anklam, E.; Deschenaux, R.; Lehn, J.-M.; Pietraskiewicz, M. Helv.
Chim. Acta 1988, 71, 1042–1052; (c) Galaup, C.; Azéma, J.; Tisnès, P.; Picard, C.;
Ramos, P.; Juanes, O.; Brunet, E.; Rodriguez Ubis, J. C. Helv. Chim. Acta 2002, 85,
1613–1625.
7. Takalo, H.; Hemmilä, I.; Sutela, T.; Latva, M. Helv. Chim. Acta 1996, 79, 789–802.
8. (a) Latva, M.; Takalo, H.; Mukkala, V.-M.; Matachescu, C.; Rodriguez-Ubis, J. C.;
Kankare, J. J. Luminescence 1997, 75, 149–169; (b) Chen, J.; Selvin, P. R. J.
Photochem. Photobiol., A 2000, 135, 27–32; (c) Yuan, J.; Matsumoto, K.; Kimura,
H. Anal. Chem. 1998, 70, 596–601; (d) Houlne, M. P.; O’Briant, S. P.; Goebel, T.;
Bornhop, D. J. Anal. Chim. Acta 1999, 397, 267–278; (e) Bornhop, D. J.; Hubbard,
D. S.; Houlne, M. P.; Adair, C.; Kiefer, G. E.; Pence, B. C.; Morgan, D. L. Anal. Chem.
1999, 71, 2607–2615.
9. (a) Handl, H. L.; Gillies, R. J. Life Sciences 2005, 77, 361–371; (b) Roda, A.;
Guardigli, M.; Ziessel, R.; Mirasoli, M.; Michelini, E. Musiani Microchem. J. 2007,
85, 5–12.
10. (a) Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B. Chem. Rev. 1999, 99,
2293–2352; (b) Caravan, P. Acc. Chem. Res. 2009, 42, 851–862; (c) Aime, S.;
Delli Castelli, D.; Crich, S. G.; Gianolio, E.; Terreno, E. Acc. Chem. Res. 2009, 42,
822–831.
Finally, we succeeded in grafting a diamine under the condi-
tions of carboamidation using ligand 9 and large excess of 2,20-
(ethylenedioxy)bis(ethylamine). Compound 18 was conveniently
isolated and used in a Schotten–Bauman peptidic coupling reac-
tion20 with
D-(+)-Biotin, allowing isolation of compound 19, an
interesting ligand for lanthanide complexation and FRET experi-
ments based on avidin or streptavidin recognition events
(Scheme 5).21 No racemization of the Biotin fragment is observed
during this set of reactions.
11. (a) Jacques, V.; Desreux, J. F. Top Curr. Chem. 2002, 221, 123–164; (b) Datta, A.;
Raymond, K. N. Acc. Chem. Res. 2009, 42, 938–947; (c) De Leon-Rodriguez, L. M.;
Lubag, A. J. M.; Malloy, C. R.; Martinez, G. V.; Gillies, R. J.; Sherry, A. D. Acc.
Chem. Res. 2009, 42, 948–957.
In short, we have developed straightforward protocols for the
chemical modification of bis(methylamino)pyridine based ligands
with phosphonate, phosphonic acid and mixed phosphonate/car-
boxylate modules. The presence of the naphthalene subunit has
been designed to serve as antennae to promote efficient photon
absorption and energy transfer to the luminescent lanthanide cen-
tres. The long emission lifetimes in the ms range and the high
quantum yields displayed by the emergent lanthanide complexes
of these ligands make them excellent candidates for bioconjuga-
tion and use in time-resolved fluoroimmunoassays. The synthesis
and spectroscopic properties of the complexes and their applica-
tions will be disclosed in forthcoming papers.
12. Fleisch, H. Medicina 1997, 57, 65–75.
13. (a) Aime, S.; Botta, M.; Garino, E.; Crich, S. G.; Giovenzana, G.; Pagliarin, R.;
Palmisano, G.; Sisti, M. Chem. Eur. J. 2000, 6, 2609–2617; (b) Charbonnière, L.
C.; Schurhammer, R.; Mameri, S.; Wipff, G.; Ziessel, R. F. Inorg. Chem. 2005, 44,
7151–7160; (c) Safiulina, A. M.; Sinegribova, O. A.; Matveena, A. G.; Goryunov,
E. I.; Grigoriev, M. S.; Nifant’ev, E. E.; Tananaev, I. G. Russ. J. Inorg. Chem. 2012,
57, 108–114.
14. Cristau, H.-J.; Brahic, C.; Pirat, J.-L. Tetrahedron 2001, 57, 9149–9156.
15. Franz. J. E. Ger. Offen. 2152826, 1972; Chem. Abstr. 1972, 77, 1605079k.
16. Brelière, J. C.; Edmonds-Alt, X.; Garcia, G. EP 100718, 1983; Chem. Abstr. 1984,
100, 192078j.
17. Benniston, A. C.; Mitchell, S.; Rostron, S. A.; Yang, S. Tetrahedron Lett. 2004, 45,
7883–7885.
18. Takalo, H.; Pasanen, P.; Kankare, J. Acta Chem. Scand. 1988, 373–377.
19. Chougrani, K.; Niel, G.; Boutevin, B.; Beilstein, David G. J. Org. Chem. 2011, 7,
364–368. and references therein.
Acknowledgments
20. Carpino, L. A.; Cohen, B. J.; Stephens, K. E.; Sadat-Aalaee, Y.; Tien, J.; Langridge,
D. C. J. Org. Chem. 1986, 51, 3732–3734.
21. (a) Florin, E. L.; Moy, V. T.; Gaub, H. E. Science 1994, 264, 415–417; (b) Pierres,
A.; Touchard, D.; Benoliel, A.-M.; Bongrand, P. Biophys. J. 2002, 82, 3214–3223.
We thank the Centre National de la Recherche Scientifique
(CNRS) and the European Commission for financial support of MS