4th EucheMs chemistry congress

Monday, 27-Aug 2012
s785
chem. Listy 106, s587–s1425 (2012)
organic Chemistry, Polymers – ii
Physical organic methods – iii
o - 0 9 4
MiCrowAveS And MuLti-CoMPonent
reACtionS in the SyntheSiS of MediuM-Sized
rinGS
e. vAn der eyCKen 1
1 KU Leuven BE0419052173, Chemistry, Leuven, Belgium
Medium-sized rings are abundantly present in many
biologically active (natural) products as e.g. the alkaloids
aphanorphine, lennoxamine and cephalotaxine and the
noncompetitive N-methyl-D-aspartate (NMDA) receptor
antagonist Dizocilpine, also known as MK-801. However, the
synthesis of medium-sized rings is known to be rather
cumbersome and no good generally applicable procedures have
been described so far. Some time ago we have elaborated an
efficient synthesis of the 3-benzazepine framework via an
intramolecular Heck reductive cyclization. We have demonstrated
that the application of microwave irradiation is beneficial for this
process. As a result of these investigations we extended our
research towards the synthesis of indoloazocines,
dibenzoazocines, dibenzoazepines, 3-benzazepines and
dibenzo[c,e]azepinones. To assure the generation of diversity we
utilized multicomponent reactions as the aldehyde/amine/alkyne
(A3) coupling and the Ugi 4CR which will be run in an
intramolecular fashion. The beneficial effect of the application of
microwave irradiation in each of these processes will be
commented.
references:
1. Efficient Synthesis of the 3-Benzazepine Framework via
Intramolecular Heck Reductive Cyclization, P. A. Donets,
E. Van der Eycken, Org. Lett., 9, 3017-3020, 2007.
2. Unprecedented Cu(I)-Catalyzed Microwave-Assisted
Three-Component Coupling of a Ketone, an Alkyne
and a Primary Amine, O. P. Pereshivko, V. A. Peshkov,
E. V. Van der Eycken, Org. Lett., 12, 2638-2641,
2010 and references cited.
3. A walk around the A3-coupling reaction and related
protocols, V. A. Peshkov, O. P. Pereshivko,
E. V. Van der Eycken, Chem. Soc. Rev.,
DOI:10.1039/C2CS15356D, 2012
Keywords: Microwave chemistry; Medium-ring compounds;
Multi-component reactions;
Physical organic methods – iii
4 th EucheMs chemistry congress
o - 0 9 5
PhoSPhoreSCent iridiuM CoMPLexeS
ConJuGAted to CxCr4-tArGetinG PePtideS
for LifetiMe iMAGinG
J. KuiL 1 , P. SteunenBerG 2 , P. Chin 1 , K. JALinK 3 ,
A. veLderS 4 , f. vAn Leeuwen 1
1 Leiden University Medical Center, Radiology, Leiden,
Netherlands
2 Wageningen University, Laboratory of Organic Chemistry,
Wageningen, Netherlands
3 Netherlands Cancer Institute – Antoni van Leeuwenhoek
Hospital, Cell Biology I, Amsterdam, Netherlands
4 Wageningen University, BioNanoTechnology, Wageningen,
Netherlands
Fluorescence lifetime imaging microscopy (FLIM) is an
optical imaging technique that produces contrast based on
differences in luminescence decay rates (lifetime). Standard
organic dyes such as fluorescein generally have lifetimes
of < 10 ns, which is also the case for autofluorescence generated
by cells and tissue. On the other hand, transition metal complexes
possess lifetimes of > 100 ns, which makes discrimination from
autofluorescence unambiguous. To benefit from these long
lifetimes in targeted imaging applications, we have prepared
phosphorescent iridium(III) complexes for chemokine receptor
4 (CXCR4) targeting. CXCR4 over-expression is found in many
types of cancer, where it plays a role in, among others, the
metastatic spread. For this reason it is an interesting biomarker
for the field of molecular imaging. [1]
Three iridium complexes, containing one, two or three
β-alanine spacers, were synthesized. [2] They had luminescent
lifetimes of 200-220 ns, absorption maxima of approximately
400 nm and emission maxima of approximately 570 nm. The
iridium complexes were functionalized with one, two or three
targeting peptides to allow for CXCR4 visualization. The CXCR4
receptor affinities of the mono-, di- and trimeric peptide
derivatives were determined using flow cytometry and amount
84.4, 254.4 and 66.3 nM, respectively. All three derivatives did
not cause cytotoxicity up to 3 µM concentrations and could
distinguish between cell lines with different CXCR4 expression
levels. FLIM showed that the peptide–iridium complex conjugates
can be used to visualize CXCR4 expression in tumor cells with
very high contrast. [3]
references:
1. Kuil, J., Buckle, T., van Leeuwen, F.W.B., Chem. Soc.
Rev., accepted
2. Steunenberg, P., Ruggi, A., van den Berg, N.S., Buckle, T.,
Kuil, J., van Leeuwen, F.W.B., Velders, A.H., Inorg.
Chem., 2012, 51, 2105-2114
3. Kuil, J., Steunenberg, P., Chin, P.T.K., Oldenburg, J.,
Jalink, K., Velders, A.H., van
Leeuwen, F.W.B., ChemBioChem, 2011, 12, 1897-1903
Keywords: Luminescence; Metal-organic frameworks;
Peptides; Fluorescence spectroscopy; Synthesis design;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc