η6-(Arene)tricarbonylchromium and manganese complexes linked to 2′-deoxyuridine

Article abstract of DOI:10.1021/om700674v

Synthesis of η⁶-(arene)tricarbonylchromium and manganese complexes linked to 2′-deoxyuridine via a triple-bond spacer is reported using palladium-catalyzed reactions of alkynes with halogeno derivatives, and their antiviral activity in cell-based assays studied.

Full text of DOI:10.1021/om700674v

Organometallics 2007, 26, 5727-5730
5727
η6-(Arene)tricarbonylchromium and Manganese Complexes Linked
to 2′-Deoxyuridine
Me´lanie Etheve-Quelquejeu,† Jean-Philippe Tranchier,‡ Franc¸oise Rose-Munch,*,‡
Eric Rose,*,‡ Lieve Naesens,§ and Erik De Clercq§
UMR CNRS 7613, Synthe`se, Structure et Fonction de Mole´cules BioactiVes, UMR CNRS 7611, Laboratoire
de Chimie Organique, UniVersite´ P. et M. Curie, Paris 6, Tour 44, 1er Et., Case 181, 4 Place Jussieu,
75252 Paris Cedex 05, France, and Rega Institute for Medical Research, Katolieke UniVersiteit LeuVen,
B-3000, LeuVen, Belgium
ReceiVed July 5, 2007
Summary: Synthesis of η6-(arene)tricarbonylchromium and man-
ganese complexes linked to 2′-deoxyuridine Via a triple-bond
spacer is reported using palladium-catalyzed reactions of
alkynes with halogeno deriVatiVes, and their antiViral actiVity
in cell-based assays studied.
literature when spaced by a thymine PNA monomer.10 Mann
et al. have also shown recently that ruthenium complexes can
serve as CO-releasing molecules in ViVo, thereby suppressing
organ graft rejection and protecting tissues from ischemic injury
and apoptosis.11 Thus, we deemed interesting trying to synthe-
size 2′-deoxyuridine derivatives whose C5 atom carbon would
be substituted by arenetricarbonylchromium12 and -manganese
complexes,13 as electron-withdrawing groups, via a triple bond.
Indeed, the salient feature of η6-arenetricarbonylchromium
complexes and isoelectronic cationic η6-arenetricarbonylman-
ganese complexes is their very high electrophilicity due to the
decreased electron density of the arene ring coordinated to the
M(CO)3 entity. The reactivity study of such complexes allowed
the development of unprecedented reactions with significant
Introduction
In recent years, there has been remarkable interest in
nucleosides in which the base unit has been modified to provide
new and unique biological and chemical properties. Of particular
interest has been the generation of pyrimidine analogues
substituted at the C5-position of the heterocycle, especially those
in the 2′-deoxyuridine series. Indeed they have been investigated
as antiviral and anticancer agents.1 In particular, 5-alkynyl-
2′deoxyuridine derivatives have been reported and evaluated
as potential antiviral agents,2 and the structure-activity relation-
ship studies seem to indicate that the C-5 substituents likely to
confer activity are those that are electron-withdrawing and
conjugated to the heterocycle.3
(4) (a) Meade, T. J.; Kayyem, J. F. Angew. Chem., Int. Ed. Engl. 1995,
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Schlawe, D.; Majdalani, A.; Velcicky, J.; Hebler, E.; Wieder, T.; Prokop,
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Acids Res. 2002, 30, e58.
It is noteworthy that, whereas ruthenium,4,5 osmium,5 iron,6
rhodium,7 technetium,8 or platinum9a complexes have already
been incorporated into nucleosides or nucleotides, chromium
and manganese complexes have never been used as monomers
before. To our knowledge, only one example of synthesis of
chromium tricarbonyl derivatives has been described in the
* Corresponding author. E-mail: rosemun@ccr.jussieu.fr; rose@
ccr.jussieu.fr.
† UMR CNRS 7613, Synthe`se, Structure et Fonction de Mole´cules
Bioactives.
‡ Universite´ P. et M. Curie,
§ Katolieke Universiteit Leuven.
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10.1021/om700674v CCC: $37.00 © 2007 American Chemical Society
Publication on Web 10/05/2007

5728 Organometallics, Vol. 26, No. 23, 2007
Notes
Scheme 1
Scheme 3
Scheme 2
Scheme 4
applications in organic and organometallic syntheses. Among
them, in the chromium series, nucleophilic aromatic substitutions
SNAr of the X group by a nucleophile Nu- ipso (on the carbon
bearing the leaving group),14 cine (ortho to the leaving group),15
tele-meta (meta to the leaving group),16 and tele-para (para to
the leaving group)17 have been well developed as well as
palladium-catalyzed reactions,18 which enable ready access to
a large variety of substituted complexes bearing R groups such
as alkyl groups, double- and triple-bond-linked to the π-system,
Scheme 1.
More recently, in the manganese series, analogous reactions
have been established starting from neutral η5-cyclohexadienyl-
tricarbonylmanganese complexes, easily obtained by addition
of a nucleophile to the corresponding cationic complex, Scheme
2. Thus, we reported cine and tele nucleophilic substitutions
occurring when the η5-cyclohexadienyl complex is treated with
H- and then with H+, path a,19 as well as Pd-cross-coupling
reactions, path b,20 R ) alkyl, alkene, alkyne groups, Scheme 2.
In both cases (Cr and Mn), we reported also a general strategy
to synthesize conjugated dinuclear organometallic complexes12g,21
using a palladium-catalyzed coupling reaction. In the present
work, we applied the Sonogashira coupling reaction22 in order
to link η6-chromium complexes as well as η5- and η6-manganese
complexes to 2′-deoxyuridine derivatives, and we report here
the results of our study.
Results and Discussion
For our strategy of coupling reaction, we chose, as starting
material, η6-chromium A and η5-manganese complexes B,
bearing a triple bond, and, as the halogeno-substituted partner,
the commercially available iodo derivative C, Scheme 3.
Coupling of Chromium Complexes. Sonogogashira cou-
pling between the 5-iodo-2′-deoxyuridine 1a with η6-(phenyl-
ethynyl)tricarbonylchromium complex 2a, easily obtained ac-
cording to literature procedure,21a,23,24 in the presence of
Pd(PPh3)4 and CuI in Et3N/THF at reflux or Pd2dba3 and AsPh3
in THF/Et3N at 50 °C, gave an intractable product mixture,
Scheme 4. The use of the resin “Amberlite IRA-67” in
Sonogashira cross couplings with polar nucleosides recently
published25 appeared to be promising because the separation
from the reaction mixture involves only filtration. Indeed
Amberlite IRA-67 is a weakly basic gel with a tertiary amine
functionality and thus suitable as a heterogeneous base in the
coupling reaction. However, the expected coupling product 3a
was obtained in a poor yield (13%) with decomplexed com-
pounds in DMF as solvent, which probably decoordinates the
Cr(CO)3 entity. We therefore found that an appropriate mixture
of MeOH in CH2Cl2 in a 1:4 ratio could dissolve the nucleoside
and permitted performing the coupling reaction, giving complex
3a in 40% yield with less decomplexation. Furthermore when
the reaction was run with the protected nucleoside 1b (R )
Bz), Pd2dba3, and AsPh3 in THF/Et3N at 50 °C for 1 h, complex
3b was isolated in 76% yield, Scheme 4.
(13) (a) Mc Daniel, K. In ComprehensiVe Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, U.K.,
1995; Vol. 6, Chapter 4, p 93. (b) Pike, R. D.; Sweigart, D. A. Coord.
Chem. ReV. 1999, 187, 183. (c) Planas, J. G.; Prim, D.; Rose-Munch, F.;
Rose, E.; Monchaud, D.; Lacour, J. Organometallics 2001, 20, 4107. (d)
Oh, M.; Carpenter, B.; Sweigart, D. A. Acc. Chem. Res. 2004, 37, 1. (e)
Sweigart, D. A.; Reingold, J. A.; Son, S. U. Manganese Compounds
Containing CO Ligands. In ComprehensiVe Organometallic Chemistry, 3rd
ed.; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier: Oxford, 2006; Vol.
5, Chapter 10, pp 761-814,
The main spectroscopic features of arenetricarbonylchromium
complexes are the presence of two strong A1 and E carbonyl
ligand stretching bands26 in the IR spectra and a remarkable
(14) (a) Rose-Munch, F.; Aniss, K.; Rose, E. J. Organomet. Chem. 1990,
385, C1. (b) Rose-Munch, F.; Aniss, K.; Rose, E.; Vaissermann, J. J.
Organomet. Chem. 1991, 415, 223.
(15) (a) Rose-Munch, F.; Rose, E. Semra, A. Chem. Commun. 1986,
1551. (b) Rose-Munch, F.; Rose, E.; Semra, A.; Jeannin, Y.; Robert, F. J.
Organomet. Chem. 1988, 353, 53. (c) Rose-Munch, F.; Rose, E.; Semra,
A.; Bois, C. J. Organomet. Chem. 1989, 363, 103. (c) Rose-Munch, F.;
Rose, E.; Semra, A. J. Organomet. Chem. 1989, 377, C9. (d) Djukic, J. P.;
Rose-Munch, F.; Rose, E. Chem. Commun. 1991, 22, 1634. (d) Rose-Munch,
F.; Bellot, O.; Mignon, L.; Semra, A.; Robert, F.; Jeannin, F. J. Organomet.
Chem. 1991, 402, 1.
(16) (a) Boutonnet, J. C.; Rose-Munch, F. Rose, E. Tetrahedron Lett.
1985, 26, 3989. (b) Rose-Munch, F.; Rose, E.; Semara, A. Chem. Commun.
1986, 1108. (c) Boutonnet, J. C.; Rose-Munch, F.; Rose, E.; Semra, A.
Bull. Soc. Chim. Fr. 1987, 640. (d) Rose-Munch, F.; Rose, E.; Semra, A.;
Garcia-Oricain, J.; Knobler, C. J. Organomet. Chem. 1989, 363, 297. (e)
Djukic, J. P.; Rose-Munch, F.; Rose, E. Organometallics 1995, 14, 2027.
(17) Rose-Munch, F.; Rose, E.; Semra, A. Chem. Commun. 1987, 942.
(18) Prim, D.; Tranchier, J. P.; Rose-Munch, F.; Rose, E. Eur. J. Inorg.
Chem. 2000, 901.
(19) Balssa, F.; Gargliadini, V.; Rose-Munch, F.; Rose, E. Organome-
tallics 1996, 15, 4373.
(20) Aufrant, A.; Prim, D.; Rose-Munch, F.; Rose, E.; Schouteeten, S.;
Vaissermann, J. Organometallics 2003, 22, 1898.
(21) (a) Schouteeten, S.; Tranchier, J. P.; Rose-Munch, F.; Rose, E.;
Aufrant, A. Organometallics 2004, 23, 4308. (b) Jacques, B.; Tranchier, J.
P.; Rose-Munch, F.; Rose, E.; Stephenson, G. R.; Guyard-Duhayon, C.
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50, 4467. (b) Sonogashira, K. In ComprehensiVe Organic Chemistry; Trost,
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B. M. Chem. Commun. 2005, 4551.

Notes
Organometallics, Vol. 26, No. 23, 2007 5729
Scheme 5
Scheme 6
shielding effect of the Cr(CO)3 entity on the aromatic proton
1
resonances in the H NMR spectra.27 For complex 3a, two
infrared CO bands appear at 1955 and 1863 cm-1 in the solid
1
state (IR ATR). The H NMR spectrum displays three well-
resolved signals of the five aromatic ring protons at 5.74 (ortho
protons), 5.54 (meta protons), and 5.46 ppm (para protons) in
MeOD, in good agreement with a conformation of the major
conformer of the Cr(CO)3 tripod anti-eclipsing the triple
bond.12e,f,28 For complex 3b, the IR spectrum shows two
Scheme 7
1
stretching bands at 1961 and 1878 cm-1 and the H NMR
exhibits the five aromatic proton signals at 5.26 ppm as a broad
multiplet.
The protected nucleoside 1b, outperforming the alcohol 1a,
was chosen as the halogeno substrate to carry out the next
experiment. For this purpose, another ethynyl chromium
complex was synthesized for the first time: the η6-(3-methyl-
phenylethynyl)tricarbonylchromium complex 2b obtained by
Pd-catalyzed reaction between η6-(3-methylchlorobenzene)-
tricarbonylchromium complex 2d15b and trimethylsilylacetylene
TMSA in the presence of CuI, Pd(PPh3)2Cl2 in THF, and NEt3,
Scheme 5. The expected η6-(1-trimetylsilylethynyl-3-methylphe-
nyl)tricarbonylchromium complex 2c, quantitatively obtained,
was desilylated with MeOH and MeONa to afford the yellow-
orange solid 2b in 90% yield. Under the same experimental
conditions as those used for the formation of 3b, condensation
of 2b with 5-iodo-2′-deoxyuridine 1b afforded complex 3c in
55% yield, Scheme 4. Selected IR and NMR data display two
bands at 1957 and 1871 cm-1 and two aromatic signals at 5.57
(1H, t) and 5.30 ppm (3H, m), respectively, in good agreement
with the proposed structure.
Coupling of Manganese Complexes. Several years ago we
showed that the oxidative addition of a stoichiometric amount
of Pd(PPh3)4 to the C-Cl bond of the cationic η6-(4-chloro-
anisole)tricarbonylmanganese complex 429 proceeds readily at
room temperature to give the square-planar Pd complex 5 with
two cis phosphorus ligands. However, in contrast to the
tricarbonylchromium analogue, the dinuclear complex 5 is
unreactiVe toward CO and a nucleophile probably because of
the strong electron-withdrawing effect of the Mn(CO)3+ entity,
Scheme 6 path a. In other words, the only way to link the
cationic η6 Mn complex 4 to the iodo substrate 1b via a triple
bond was to involve the alkyne-substituted η5-complex 8a,20,21a
Scheme 6. The Sonogashira coupling reaction of this last
compound with the iodo deoxyuridine derivative C, Scheme 3,
C ) ArI, should be facilitated, giving access to the η5-complex
9. At this stage, the rearomatization by exo hydrogen abstraction,
using trityl tetrafluoroborate,21a should form the desired η6 Mn
complex 10, Scheme 6.
Thus, the starting (η5-cyclohexadienyl)tricarbonylmanganese
complexes were prepared by adding a hydride30 or a Grignard
reagent, Scheme 6.19,20,31,32 Addition of LiAlH4 or PhMgBr to
the η6-Mn complex 4 gave regioselectively 6a,20 which corre-
sponds to a meta addition with respect to the methoxy group in
99% yield for Nu ) H, and 6b20 in 91% yield for Nu ) Ph. A
coupling reaction with trimethylsilylacetylene yielded the cor-
responding η5-cyclohexadienylMn(CO)3 7a (Nu ) H in 97%
yield) and 7b (Nu ) Ph in 91% yield. The required alkynyl-
substituted cyclohexadienyl-Mn complexes 8a,21a as a yellow
oil in 99% yield, and 8b,20 as a yellow oil in 91% yield, may
be prepared by literature methods as indicated in Scheme 6.
The reaction of the η5-Mn complex 8a and the 5-iodo-2′-
deoxyuridine 1a, using the experimental procedure previously
described in the case of areneCr(CO)3/Pd(PPh3)4, CuI, Amberlite
IRA-67, CH2Cl2/MeOH as solvent at 35 °C, gave in a low yield
complex 9a, which was difficult to purify, Scheme 7. However,
the reaction of 8a or 8b with the protected nucleoside 1b led to
the expected products 9b and 9d in 65% and 58% yield,
respectively. IR data of the dibenzoyl manganese complexes
9b and 9d showed bands at 1919 and 2010 cm-1 and 1924 and
2011 cm-1, respectively. The 1H NMR data in CDCl3 of these
two complexes showed four signals at 4.97 and 5.13 (H10, 1:1
ratio of two diastereoisomers due to the presence of central and
planar chiralities of the η5-cyclohexadienyl complexes), 5.72
(H11), and 2.99 (H13) for 9b and at 4.97 and 5.17 (H10, 1:1
ratio of two diastereoisomers), 5.57 (H11), and 3.50 (H13) for
9d, in good agreement with shielded signals of the protons H13
at the end of the conjugated η5-system, which have a less
pronounced sp2 character. Furthermore, only the H14endo proton
(26) (a) Van Meurs, F.; Baas, J. M. A.; Van Bekkum, H. J. Organomet.
Chem. 1976, 113, 353. (b) Solladie´-Cavallo, A. Polyhedron 1985, 4, 901.
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Bekkum, H. J. Organomet. Chem. 1976, 113, 341.
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Int. Ed. 2006, 45, 3481.

5730 Organometallics, Vol. 26, No. 23, 2007
Notes
MS (FAB+): m/z 673 (M + 1), 537 (M + 1 - Cr(CO)3)). Anal.
Calcd for C34H25N2CrO10: C, 60.71; H, 3.60. Found: C, 61.03; H,
3.81.
of complex 9b appears as two signals of equal importance at
2.63 and 2.76 ppm, whereas the analogous proton of complex
9d is not affected by the planar chirality and exhibits a signal
at 4.00 ppm. We recover also deprotected compounds 9a and
9c by hydrolysis of the esters 9b and 9d with MeONa in MeOH
in 98% and 54% yield, respectively.
3′,5′-Dibenzoyl-5-(tricarbonyl(η5-1-ethynyl-4-methoxycyclo-
hexa dienyl)manganese)-2′-deoxyuridine, 9b. Tricarbonyl(η5-1-
methoxy-4-ethynylcyclohexadienyl)manganese (8a)20,21 (0.072 g,
0.264 mmol), 3′,5′-dibenzoyl-5-iodo-2′-deoxyuridine (1b) (0.136
g, 0,24 mmol), Pd2(dba)3 (0.022 g, 0.024 mmol), and AsPh3 (0.022
g, 0.072 mmol) were introduced into a flask. Under N2, 10.0 mL
of Et3N and 5.0 mL of THF were added and stirred at 50 °C for 1
h. The brown suspension was filtered on Celite (eluted with Et2O
and AcOEt), the solvent was evaporated under reduced pressure,
and the crude product was purified on a silica gel chromatography
column (Merck silica gel 60, 15-40 µm, petroleum ether/ethyl
acetate, 3:2). After evaporation under reduced pressure and drying
in Vacuo, an orange-brown solid was obtained (0.110 g, 0.156
mmol, 65%). mp ) 210 °C. IR: ν (cm-1) 2014 (CO-Mn), 1927
Therefore, with complex 9b in hand, we attempted hydride
-
abstraction of the exo hydrogen using CPh3+BF4 in CH2Cl2,
at room temperature for 1 h, and we were pleased to obtain the
-
η6-(arene)Mn+(CO)3, BF4 complex 10b in 76% yield as a
yellow solid, Scheme 7. The IR data are consistent with the
rearomatization of the η5-system into a η6 one. Indeed, the
1
stretching bands occurred at 2037 and 2011 cm-1. H NMR
signals of the aromatic protons of this para-disubstituted arene
complex appear at 6.62 ppm for H11 and H13 protons and at
7.06 and 7.16 ppm as two distinct doublets for the diastereotopic
H10 and H14 protons.
1
(CO-Mn), 1716 (CO). H NMR (200 MHz, CDCl3): δ 8.24 (s,
The complexes 3a, 9a, and 9c were evaluated for their
antiviral activity in cell-based assays measuring the compounds’
inhibitory effect on the virus-induced cytopathic effect. Unfor-
tunately, the compounds were found to be inactive against DNA
viruses such as vaccinia virus or human herpes viruses (i.e.,
herpes simplex virus type 1, cytomegalo virus, and varicella
zoster virus) and various RNA viruses (i.e., human influenza
viruses; vesicular stomatitis virus; parainfluenza virus-3 virus;
Sindbis virus; Coxsackie virus B4, and Punta Toro virus). One
compound, 9c, had minimal activity against respiratory syncytial
virus.
1H, NH), 8.04 (m, 4H, Ph), 7.79 (7.77) (s, 1H, H6), 7.60-7.38 (m,
6H, Ph), 6.34 (m, 1H, H1′), 5.72 (m, 1H, H11), 5.60 (m, 1H, H3′),
5.10 (4.96) (m, 1H, H10), 4.72 (m, 3H, H4′, H5′), 3.43 (s, 3H, OCH3),
2.99 (m, 1H, H13), 2.76 (2.63) (m, 2H, H14endo, H2b′), 2.31 (m, 2H,
H
14exo, H2a′). 13C NMR (100 MHz, CDCl3): δ 165.8 (CO), 159.7
(C4), 149.1 (C2), 143.1 (C6), 140.7 (C12), 129.7, 129.1, 129.0, 128.7,
128.6, 128.5 (Ar), 100.9 (C5), 97.2 (C10), 95.0, 94.8 (C7, C8), 86.2
(C1′), 83.2 (C4′), 75.0 (C3′), 68.1 (C11), 64.4 (C5′), 54.3 (OCH3),
45.3 (C9), 38.5 (C2′), 36.3 (C13), 31.4 (31.6) (C14). Anal. Calcd for
C35H27MnN2O11: C, 59.48; H, 3.85. Found: C, 59.32; H, 4.03.
HRMS: calcd for C35H27MnN2O11Na, 729.0893; found, 729.0899
[M + Na]+.
3′,5′-Dibenzoyl-5-(tricarbonyl(η6-1-ethynyl-4-methoxybenzen-
e)manganese)-2′-deoxyuridine Tetrafluroborate, 10b. To a solu-
tion of 3′,5′-dibenzoyl-5-(tricarbonyl(η5-1-ethynyl-4-methoxycy-
clohexadienyl)manganese)-2′-deoxyuridine (9b) (0.159 g, 0.225
mmol) in 5 mL of CH2Cl2 was added CPh3BF4 (0.148 g, 0.45 mmol)
in 5 mL of CH2Cl2. The mixture was stirred at rt for 1 h. The
product was precipitated by adding 30 mL of dry Et2O, filtered,
washed with Et2O, and dried in Vacuo. A pale yellow, oily solid
was obtained (0.120 g, 0.170 mmol, 76%). IR ν (cm-1): 2037
Conclusion
We successfully developed the first syntheses of η6-(arene)-
tricarbonylchromium and -manganese complexes linked to a
nucleoside spaced by an alkyne using Sonogashira Pd-catalyzed
reactions between η6-(ethynylphenyl)tricarbonylchromium and
η5-(ethynylcyclohexadienyl)tricarbonylmanganese complexes
and 5-iodo-2′-deoxyuridine. Although the compounds presented
here were found to have no antiviral activity, the possibility to
introduce at the strategic 5-position such highly electrophilic
organometallic complexes, which are very useful building blocks
in organic synthesis, opens new perspectives in the chemical
synthesis of new nucleoside analogues.
(CO-Mn), 2011 (CO-Mn), 1717 (CO), 1690 (CO). [R]20 -89
D
1
(c 0.82, CHCl3). H NMR (400 MHz, (CD3)2CO)): δ 10.59 (s,
1H, NH), 8.36 (s, 1H, H6), 8.13 (m, 4H, Ph), 7.80-7.50 (m, 6H,
Ph), 7.22-7.01 (m, 2H, H10, H14), 6.62 (m, 2H, H11, H13), 6.41 (t,
J ) 6.8 Hz, 1H, H1′), 5.80 (m, 1H, H3′), 4.79 (m, 3H, H4′, H5′),
4.26 (s, 3H, OCH3),2.89 (m, 2H, H2′). 13C NMR (100 MHz, (CD3)2-
CO)): δ 215.1 (CO-Mn), 165.0 (CO), 160.0 (C4), 148.4 (C2), 146.4
(C12), 142.0 (C6), 133.6, 133.0, 129.7, 128.9 (Ar), 114.2 (C9), 105.0
(C10, C14), 92.8, 92.0, 89.9 (C5, C7, C8), 87.1 (C1′), 83.1 (C11, C13),
83.0 (C4′), 75.2 (C3′), 64.6 (C5′), 55.0 (OCH3), 37.9 (C2′). Anal.
Calcd for C35H26BF4N2MnO11: C, 53.02; H, 3.31. Found: C, 53.28;
H, 3.42. HRMS-ES: calcd for C35H26BF4N2MnO11, 792.0946; calcd
for C35H26N2MnO11 705.0917; found 705.0912 [M - BF4]; found
566.1581 [M - BF4 - Mn(CO)3 + Na]+.
Experimental Section
General Procedure. 3′,5′-Dibenzoyl-5-(tricarbonyl(η6-ethy-
nylphenyl)chromium)-2′-deoxyuridine, 3b. Tricarbonyl(ethynyl-
benzene)chromium (0.139 g, 0.585 mmol), Pd2(dba)3 (0.049 g,
0.053 mmol), AsPh3 (0.049 g, 0.160 mmol), and 3′,5′-dibenzoyl-
5-iodo-2′-deoxyuridine (1b) (0.299 g, 0.52 mmol) were introduced
into a flask and dissolved in 20 mL of Et3N and 10 mL of THF.
The reaction mixture was stirred for 1 h at 50 °C and filtered on
Celite (eluated with Et2O and AcOEt). The solvent was evaporated
under reduced pressure. The crude product was purified on a silica
gel chromatography column (Merck silica gel 60, 15-40 µm,
petroleum ether/AcOEt, 7:3). After evaporation under reduced
pressure and drying in Vacuo, a red complex was obtained (0.272
g, 0.400 mmol, 76%). mp ) 126 °C. IR ν (cm-1): 1961 (CO-
Cr), 1878 (CO-Cr), 1710 (CO). [R]20D -130 (c 0.74, CHCl3). 1H
NMR (400 MHz, CDCl3): δ 8.26 (s, 1H, NH), 8.03 (m, 4H, Ph),
7.98 (s, 1H, H6), 7.65-7.43 (m, 6H, Ph), 6.36 (m, 1H, H1′), 5.61
(m, 1H, H3′), 5.40-5.10 (m, 5H, H10, H11, H12, H13, H14), 4.80-
4.61 (m, 3H, H5′, H4′), 2.83 (m, 1H, H2a’), 2.36 (m, 1H, H2b′). 13C
NMR (100 MHz, CDCl3): δ 232.0 (CO-Cr), 165.9 (CO), 160.1
(C4), 149.1 (C2), 142.6 (C6), 133.8, 129.8, 129.2, 128.9, 128.8, 128.6
(Ar), 94.4, 91.6, 89.8 (C10, C11, C12), 90.3, 89.6, 80.0 (C7, C8, C9),
86.4 (C1′), 83.4 (C4′), 75.0 (C3′), 65.8 (C5), 64.4 (C5′), 38.8 (C2′).
Acknowledgment. We thank Jasmin Nitsche, Hamburg,
University and Ulrike Ziffels, Bonn University, for helpful
synthesis and the CNRS for financial support.
Supporting Information Available: Syntheses of the new
compounds except complexes 3b, 9b, and 10b. The activity of the
test compounds against a variety of DNA viruses and RNA viruses
was evaluated in cell-culture-based assays using the virus-induced
cytopathic effect as the parameter for virus replication; see
Supporting Information.1e Tables giving cytotoxicity and antiviral
activity of complexes 3a, 9a, and 9c in HEL, Vero, and HeLa cell
cultures. This material is available free of charge via the Internet
at http://pubs.acs.org.
OM700674V