N-Acetyl-5-arylidenetetramic acids: Synthesis, X-ray structure elucidation and application to the preparation of zinc(II) and copper(II) complexes

Article abstract of DOI:10.1016/j.tet.2014.02.019

A new route to N-acetyl-3-acyl-5-arylidenetetramic acids was developed and applied to the synthesis of a small library of compounds with diversity at carbon 3 of the heterocyclic ring. The 3-acetyl derivative was used as ligand for complexation with zinc(II) and copper(II) acetates. Both the ligand and the zinc complex were studied by X-ray single crystal structure analysis, the zinc complex forms ribbons by H-bonding from the ethanol to a neighbouring molecule.

Full text of DOI:10.1016/j.tet.2014.02.019

Tetrahedron 70 (2014) 2439e2443
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
N-Acetyl-5-arylidenetetramic acids: synthesis, X-ray structure
elucidation and application to the preparation of zinc(II) and
copper(II) complexes
,
a
b
c,
*
Dimitris Matiadis a , Olga Igglessi-Markopoulou , Vickie McKee , John Markopoulos
*
a National Technical University of Athens, Department of Chemical Engineering, Laboratory of Organic Chemistry, Zografou Campus, Athens 15773,
Greece
b Chemistry Department, Loughborough University, Leicestershire LE113TU, UK
c Laboratory of Inorganic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, 15771 Athens, Greece
a r t i c l e i n f o
a b s t r a c t
Article history:
A new route to N-acetyl-3-acyl-5-arylidenetetramic acids was developed and applied to the synthesis of
a small library of compounds with diversity at carbon 3 of the heterocyclic ring. The 3-acetyl derivative
was used as ligand for complexation with zinc(II) and copper(II) acetates. Both the ligand and the zinc
complex were studied by X-ray single crystal structure analysis, the zinc complex forms ribbons by H-
bonding from the ethanol to a neighbouring molecule.
Received 17 December 2013
Received in revised form 31 January 2014
Accepted 10 February 2014
Available online 19 February 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Tetramic acids
C-Acylation
Metal complexation
Nitrogen heterocycles
1. Introduction
cell walls.6 Some of the copper(II) complexes showed higher anti-
microbial activity than their parent compounds.7 Recently, Janda
Tetramic acid derivatives constitute an important class of ni-
trogen heterocycles containing the pyrrolidine-2,4-dione ring sys-
tem, known for over 100 years.1 They are commonly found in many
natural products exhibiting biological properties, including antibi-
otic, antifungal, cytotoxic and anti-HIV activities.2 Well known bi-
ologically active natural products include tenuazonic acid,3a
reutericyclin,3b equisetin,3c streptolydigin.3d
Tetramic acid divalent complexes are very attractive as drug
candidates, due to their ability to cross membranes in biological
tissues.2b,4 The common feature of metal chelating of 3-acyl and 3-
alkanoyl derivatives has been well known for decades, since the
first 3-acetyltetramic acid (tenuazonic acid) was isolated from
Alternaria and Phome sorghina contaminated grains as its Mg, Ca, Na
and K salts.5
et al.8 reported a novel tetramic acid degradation product from N-
acetylhomoserine as potent antibacterial agent and its complex
with Fe3þ. This tetramic acid binds iron with comparable affinity to
known bacterial siderophores, possibly providing an unrecognized
mechanism for iron solubilization. This discovery has stimulated
great interest in the antibiotic activity of tetramic acids9 (Fig. 1).
Moreover, bifunctional molecules that target copper or zinc are
of interest as possible therapeutic agents against Alzheimer’s Dis-
ease (AD). Targeting these chelators towards the peptide amyloid-
b
(Ab
) aggregates is a promising strategy to combat AD.10 In this
way, bioorganic and medicinal inorganic chemistry may contribute
to understanding the function of metal ions in AD and in discovery
of new therapeutic and diagnostic approaches. The appearance of
an 8-hydroxyquinoline derivative and its analogues stimulated the
interest in metal chelator drugs.11 Tetramic acids themselves have
Tests of antimicrobial activity indicated that the structure of the
acyl substituent at the N-position is crucial, and the copper com-
plexes showed increased liposolubility and permeability through
been reported to inhibit the aspartic protease b-secretase (BACE-1),
which is a recognized target for the therapy of Alzheimer’s
disease.12
Our research group has contributed significantly to the syn-
thesis and study of many heterocyclic compounds including tet-
ramic acids bearing a hydroxyalkyl or hydroxybenzyl group at C-
5,13 found in natural products, such as equisetin,3c trichosetin14a
and virgineone.14b More recently, we proposed a method for the
* Corresponding authors. Tel.: þ30 210 772 3259; fax: þ30 210 772 3072 (D.M.);
tel.: þ30 210 727 4450; fax: þ30 210 772 3072 (J.M.); e-mail addresses: matiadis@
mail.ntua.gr, dmatiadis@yahoo.gr (D. Matiadis), jmmarko@chem.uoa.gr (J.
Markopoulos).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.019

2440
D. Matiadis et al. / Tetrahedron 70 (2014) 2439e2443
O
O
OH
O
O
R
O
R'O
R
OR'
N
O
NaH, THF
NH
O
1
PhCHO
O
O
OH
R = Me
R = Ph
2a:
N
H
2b:
2c:
2d:
HO
R
R = CH2CH2CH3
R = (CH2)14CH3
O
O
N
O
Fig. 1. Structure of the quorum sensing tetramic acideFe3þ complex.
2a-d
chemoselective homogeneous catalytic hydrogenation of the ole-
finic bond of 3-arylidene group on the pyrrolidine-2,4-dione nu-
cleus, over other present reducible functions, using a ruthenium-
catalyst.15
Only a few studies in the literature have described sufficiently
the synthesis of 3-acyl-5-arylidenetetramic acids,16 the most im-
portant being 5-arylidene-3-phenyl tetramic acid, which has been
Scheme 1. Proposed methodology for synthesis of 5-arylidenetetramic acids 2aed via
4-arylidene oxazolone 1 (R0¼Me or Et).
a
-aminoacid at the same time. The oxazolone was attacked at the
carbonyl by the nucleophilic anion of the appropriate active
methylene compound (AM), formed by deprotonation of the active
methylene by NaH. The use of other bases, such as the nucleophilic
EtONa, NaOH, would involve side nucleophilic reactions and re-
moval of the acetyl group bonded with the nitrogen. The intra-
molecular cyclization of the intermediate molecule takes place in
situ, providing the desired tetramic acids.
The reactant:reagents ratio was 1:AM:NaH 1:2:2. The products
are precipitated after acidification of the resulting mixture, or
extracted. In the latter case, the crude products were purified by
column chromatography. 1H NMR experiments of the precipitated
products showed absence of the intermediate product. If the in-
termediate had not cyclized concomitantly, more potent conditions
would be needed for the cyclization step, such as the stronger base
NaOEt, which deprotects the amine from the acetyl group.
One of the active methylene compounds, the methyl hex-
adecanoylacetate, was prepared in the laboratory from Meldrum’s
acid and the corresponding acid chloride19 as it is not readily
available commercially.
designed as a glycine site N-methyl-D-aspartate (NMDA) receptor
antagonist in the treatment of neurological diseases. In these
studies, the ring nitrogen is either attached to a bulky benzoyl
group as otherwise it loses the acetyl group during the in-
corporation of the benzylidene moiety. Therefore, there is no lit-
erature reference for preparation of 5-arylidenetetramic acids
bearing the N-acetyl group, and the study of their coordination
chemistry.
Since N-acetyl, 3-acyl and 3-alkanoyl groups in tetramic acids, as
well as their complexes appear very promising for their effective-
ness towards biological targets, we aimed to prepare these de-
rivatives with a straightforward and facile method based on our
experience on these products. We focused our attention on the 5-
arylidenetetramic acid scaffold, known to occur in a range of anti-
biotically active natural products, such as pachydermin, magnesi-
din (5-ethylidene group) and penicillenols B1eB2.17
In this paper, we report the synthesis of N-acetyl-3-acyl-5-
arylidenetetramic acids along with two representative complexes
with Zn(II) and Cu(II) as possible therapeutic agents. Our strategy is
based on a C-acylation reaction between the anion of the appro-
priate active methylene compound, which provides the desired
functionalization on C-3 position and an azlactone, prepared from
N-acetylglycine.
2.2. Synthesis of complexes
The complexes [M(TAꢀ)2(EtOH)2], where M¼Zn or Cu and
TA¼N-acetyl-3-acetyl-5-arylidenetetramic acid were prepared by
reaction of the corresponding acetate and TA in EtOH under reflux
at ratio TA:M(OAc)2$xH2O¼1:2 (x¼2 for Zn and 1 for Cu). The zinc
complex is precipitated as yellow crystalline solid after 24 h at 0 ꢁC,
whereas the copper complex is precipitated as green powder a few
minutes after mixing the reactants.
2. Results and discussion
2.1. Synthesis of tetramic acids
The complex 3 was characterized by 1H, 13C NMR, IR, HRMS,
UVevis and X-ray structure analysis and the paramagnetic complex
4 was characterized by IR, HRMS, UVevis and magnetic suscepti-
bility measurements.
To reach these goals, we focused on developing a mild method,
in order not to break the sensitive N-acetyl bond. Thus, a small li-
brary of tetramic acids diverse at the C-3 carbon was prepared. The
synthetic course for tetramic acids 2aed is outlined in Scheme 1.
The N-acetyl protected tetramic acids can be prepared in just one
step from the commercially available 4-arylidene oxazolone 1.
However, to reduce the cost, we also prepared the starting material
1, since its synthesis is very easy and quick via a literature method.18
1 was chosen because it serves as both a protected and activated
2.3. X-ray diffraction analysis
The molecular structure of 2a is shown in Fig. 2. As expected, it is
the 4-enolic tautomer (Scheme 2) with an intramolecular hydrogen
bond linking the alcohol to the neighbouring carbonyl oxygen atom

D. Matiadis et al. / Tetrahedron 70 (2014) 2439e2443
2441
not planar, there is a twist of 27.42(8)ꢁ between the mean planes of
the two rings. The phenyl rings are linked by -stacking in-
p
ꢀ
teractions (C12eC16 3.382 and C13eC15 3.393 A centroidecentroid
distance 3.95 A, under symmetry operation 1þx, y, z, see Fig. 3).
ꢀ
Fig. 2. Molecular structure of 2a and its Zn(II) complex (3). Non-hydrogen atoms are
drawn with 50% probability ellipsoids and the intramolecular H-bond in 2a is shown as
a dashed line.
Fig. 3. Intermolecular interactions between molecules of 2a and its Zn(II) complex (3).
The structure of [Zn(TAꢀ)2(EtOH)2] (3) is shown in Fig. 2. The
zinc ion lies on a centre of symmetry and is six-coordinate, two TAꢀ
ions act as bidentate ligands and two ethanol molecules are co-
ordinated in the trans positions. Notably, the CeO bond lengths for
ꢀ
the coordinated TAeoxygen atoms are identical (1.253(2) A). The
complex molecules are linked into chains running parallel to the
a axis via hydrogen bonding linking the coordinated ethanol mol-
ecules to an uncoordinated carbonyl of a neighbouring molecule
ꢀ
(O30eO18 2.7070(16) A under symmetry operation ꢀx, 1ꢀy, 1ꢀz,
see Fig. 3).
2.4. Analytical data
The 1H NMR spectrum in DMSO-d6 of the Zn(II) complex con-
firms the formation of metaleoxygen bonds since the signal of the
acidic proton of the ligand (8.60 ppm) is absent in the metal
complex. The existence of the ethanol as a part of the crystal is
obvious as in the proton NMR of the pentoxide dried product, the
triplet and quintet of methyl and methylene protons appear at 1.06
and 3.45 ppm, respectively and the hydroxyl appears as a triplet at
3.34 ppm. The latter should be a singlet in liquid ethanol.
The IR absorption frequencies for the ligands and the metal
complexes were recorded in the range 4000e400 cmꢀ1. The spectra
further support the suggested molecule structures. The tetramic
acids are characterized by the appearance of the absorption bands
at 1740e1670 cmꢀ1 and 1640e1630 cmꢀ1 indicating a lactam car-
bonyl moiety and CeO stretching of the intramolecular hydrogen
Scheme 2. Tautomerism of N-acetyl-3-acyl-5-arylidenetetramic acids.
bonded carbonyl present in the enol form of
systems.
b,b
0-dicarbonyl
ꢀ
(O9eO8 2.6085(19) A). The exocyclic double bond (C5eC10
ꢀ
1.353(2) A) exhibits the Z-configuration, as expected by comparison
New bands at high frequencies (>3400 cmꢀ1) appear in the
spectra of complexed compounds, which can be assigned to the
OeH group of ethanol molecules coordinated in the crystal lattice.
with the similar pachydermin,17a where the configuration was de-
termined by 2D NMR methods in DMSO solution. The molecule is

2442
D. Matiadis et al. / Tetrahedron 70 (2014) 2439e2443
The complexation with the metals is further confirmed by the ap-
with diethyl ether and acidified with 10% hydrochloric acid. The
precipitated solid (in the case of 2a) was filtered, washed with cold
water (ꢂ2) and dried to afford the desired product as yellow solid.
In the case of the other active methylene compound products, the
aqueous phase was extracted with DCM (ꢂ3), dried with Na2SO4
and concentrated to afford the 2b as solid after 24 h of storage in
a fridge and washing with petroleum ether and diethyl ether and
the 2c and 2d as crude oily products. The latter, were purified with
column chromatography.
pearance of a band at 440 cmꢀ1 assignable to the
deformation and at 460 cmꢀ1 assignable to the
deformation.
n
(ZneO)þring
n
(CueO)þring
For the copper (II) complexes, the magnetic moment (meff¼2.2
BM) indicates that no reduction to copper (I) has occurred during
the reaction. The electronic spectra show a broad band in the range
of 580e740 nm with shoulders in the low frequency side, typical of
JahneTeller distorted six-coordinate copper (II) complexes.20
3. Conclusion
4.2.1. N-Acetyl-3-acetyl-5-benzylidenetetramic acid (2a). Yellow
solid (96 mg, 88%), mp 112e114 ꢁC, Rf 0.20 (pe/AcOEt¼3:7), lmax
(MeOH)/nm 264 (log ε 4.19) and 316 (4.26), lmax (CHCl3)/nm 288
(log ε 4.07) and 347 (4.26), nmax/cmꢀ1 3340 (m), 1740 (s), 1710 (s),
1625, 1580, 1250 (s), dH (300 MHz; CDCl3) 2.61 (3H, s, CH3COC-3),
2.62 (3H, s, CH3CON), 7.22e7.36 (6H, m, CH], Ph) and 8.67 (br, 1H,
OH), dH (300 MHz; DMSO-d6, Me4Si) 2.48 (3H, s, CH3COC-3), 2.50
(3H, s, CH3CON), 6.98 (1H, s, CH]), 7.23e7.34 (5H, m, Ph) and 8.60
(1H, br s, OH), dC (75 MHz; DMSO-d6, Me4Si) 25.4 (CH3COC-3), 26.3
(CH3CON), 101.6 (C-3), 117.7 (PhCH]), 127.6, 128.3, 128.9, 130.1,
134.6 (Ph), 134.6 (C-5), 167.6 (C-2, CH3CON), 179.3 (CH3COC-3) and
191.5 (C-4), dC (75 MHz, CDCl3) 24.6 (CH3COC-3), 26.6 (CH3CON),
102.9 (C-3), 122.9 (PhCH]), 126.9, 128.2, 129.9, 130.6 (Ph), 134.1 (C-
5), 166.3 (C-2), 168.5 (CH3CON), 182.9 (CH3COC-3) and 196.6 (C-4),
HRMS: calcd for C15H14NO4 272.0917; found 272.0929.
We have developed a convenient synthetic strategy towards
tetramic acids bearing the arylidene group at C-5 of the heterocyclic
ring. This methodology gives in high purities and yields tetramic
acids in one step using low cost reagents/reactants and can be
considered as a useful approach for the synthesis of metal co-
ordination products with potential biological activities. We expect
that this approach will find applications in the synthesis of natural
products containing the arylidene or alkylidene tetramic acid nu-
cleus. Future work in this area will rely upon their pharmaceutical
applications as therapeutic agents for Alzheimer’s disease, espe-
cially concerning the zinc and copper complexes.
4. Experimental section
4.1. General
4.2.2. Crystal data. C15H13NO4, triclinic, P1, a¼3.9451(9),
ꢀ
b¼12.195(3),ꢁ c¼14.380(3)
A,
a
¼113.488(3),
b
ꢀ
¼91.711(3),
3
ꢀ
All reagents were purchased from Aldrich, Fluka and Acros and
used without further purification. Dry THF was distilled from Na/
Ph2CO. Melting points were determined with a Gallenkamp MFB-
595 melting point apparatus. NMR spectra were recorded with
g
¼90.875(3) , V¼633.9(2) A , T¼150(2) K, ¼0.71073 A, Z¼2. 7256
l
reflections measured, 2564 unique (Rint¼0.0325), wR2¼0.1031 (all
data), R1¼0.0394 (I>2 (I)).
s
a
Varian Gemini-2000 300 MHz spectrometer operating at
4.2.3. N-Acetyl-3-benzoyl-5-benzylidenetetramic acid (2b). Yellow
solid (130 mg, 49%), mp 132 ꢁC (dec), Rf 0.16 (pe/AcOEt¼1:1), lmax
(MeOH)/nm 279 (log ε 4.39), nmax/cmꢀ1 3400 (m), 3240 (s), 1695 (s),
1660 (s), 1525, 1510, 1450 (s), dH (300 MHz; CDCl3þCD3OD) 2.08
(3H, s, CH3CON) and 7.20e7.57 (11H, m, PhCH], Ph), dC (75 MHz;
CDCl3þCD3OD) 23.0 (CH3CON), 101.7 (C-3), 124.6 (PhCH]), 127.5,
128.1, 128.6, 128.9, 129.5, 129.8, 132.2, 133.6 (Ph), 133.8(C-5), 167.4
(C-2), 170.3 (CH3CON) and 199.9 (PhCOC-3), 200.7 (C-4), HRMS:
calcd for C20H16NO4 334.1074; found 334.1080.
300 MHz (1H) and 75 MHz (13C). Chemical shifts are reported in
parts per million relative to CDCl3 (1H:
d
¼7.26 ppm, 13C:
d
¼77.16 ppm) or TMS (1H:
d
¼0.00 ppm, 13C:
¼0.00 ppm). A few
d
drops of CD3OD were added in CDCl3esample mixture, where
necessary. UV spectra were recorded with a PerkineElmer Lamda
25 spectrometer using MeOH or CHCl3 as solvents. IR spectra were
recorded on a Perkin Elmer 883 Spectrometer and on a Shimadzu
IRAffinity-1 FTIR Spectrometer using KBr pellets. The magnetic
susceptibility measurements were made using a Gouy balance at rt
using mercury tetrathiocyanatocobaltate(II), Hg[Co(NCS)4] as cali-
brant. HRMS were carried out in the department of Chemistry &
Biochemistry of the University of Notre Dame, IN, USA, with an ESI
instrument. Flash column chromatography was carried out on silica
gel Macherey-Nagel 0.063e0.2 mm/70e230 mesh.
4.2.4. N-Acetyl-5-benzylidene-3-butyryltetramic acid (2c). Purified
with column chromatography (pe/AcOEt, 7:3e1:1), white solid
(96 mg, 80%), mp 230 ꢁC (dec), Rf 0.45 before cc, 0.28 after cc (pe/
AcOEt¼1:1), lmax (MeOH)/nm 260 (log ε 4.21) and 315 (4.30), nmax
/
cmꢀ1 3450 (m), 2900 (m), 1725 (s), 1670 (s), 1610, 1470 (s), dH
(300 MHz; CDCl3þCD3OD) 0.91 (3H, t, J¼6.9 Hz, CH3CH2CH2), 1.60
(2H, m, J¼6.6 Hz, CH3CH2CH2), 2.52 (3H, s, CH3CON), 2.84 (2H,
pseudot., CH3CH2CH2), 7.02 (1H, s, CH]) and 7.12e7.26 (5H, m, Ph),
dC (75 MHz; CDCl3þCD3OD) 13.8 (CH3CH2CH2), 18.4 (CH3CH2CH2),
26.4 (CH3CON), 41.1 (CH3CH2CH2), 101.7 (C-3), 117.7 (PhCH]), 127.9,
128.4, 129.9, 130.5 (Ph), 135.2 (C-5), 169.9 (C-2), 170.0 (CH3CON),
185.1 (CH2COC-3) and 200.2 (C-4), HRMS: calcd for C17H18NO4
300.1230; found 300.1227.
X-ray data were collected at 150(2) K on a Bruker Apex II CCD
ꢀ
diffractometer using MoK
a
radiation (
l
¼0.71073 A). The structures
were solved by direct methods and refined on F2 using all the re-
flections.21 All the non-hydrogen atoms were refined using aniso-
tropic atomic displacement parameters and hydrogen atoms
bonded to carbon were inserted at calculated positions using
a riding model. The hydrogen atom bonded to O in 2a was located
from difference maps and the coordinates refined.
4.2. Synthesis of N-acetyl-5-benzylidenetetramic acids (2aed)
4.2.5. N-Acetyl-5-benzylidene-3-hexadecanoyltetramic
acid
(2d). Purified with column chromatography (pe/AcOEt, 8:2e6:4),
To a suspension of NaH (60% in mineral oil, 32 mg, 0.80 mmol) in
dry THF (1.5 mL) at 0 ꢁC and under argon atmosphere were added
dropwise 0.80 mmol of the appropriate active methylene com-
pound (ethyl acetoacetate, ethyl butyrylacetate, ethyl benzoylace-
tate or methyl hexadecanoylacetate). After stirring for 1 h, was
added 1 (74.8 mg, 0.40 mmol) at 0 ꢁC and the mixture was stirred
for 1 h at rt. The resulting mixture was concentrated, and the res-
idue was diluted with water (0.5 mL). The suspension was washed
off-white solid (73 mg, 39%), mp 134e136 ꢁC (dec), Rf¼0.19 (pe/
AcOET¼8:2), lmax (MeOH)/nm 259 (log ε 4.20) and 315 (4.30), nmax
/
cmꢀ1 3450 (m), 2900 (m), 2890, 2850, 1730 (s), 1670 (s), 1600, 1470
(s), dH (300 MHz; CDCl3þCD3OD) 0.94 (3H, t, J¼6.6 Hz, CH3CH2CH2),
1.31 (24H, s, (CH2)12), 1.67 (2H, br m, CH2CH2COC-3), 2.64 (3H, s,
CH3CON), 2.97 (2H, pseudot., CH2CH2COC-3), 7.14 (1H, s, PhCH])
and 7.24e7.38 (5H, m, Ph), dC (75 MHz; CDCl3þCD3OD) 14.2
(CH3CH2CH2), 22.7 (CH3CON), 25.2, 26.5, 29.4, 29.6, 29.7, 29.8, 32.0,

D. Matiadis et al. / Tetrahedron 70 (2014) 2439e2443
2443
34.6, 39.3 [(CH2)14], 101.7 (C-3), 117.8 (PhCH]), 127.9, 128.5, 130.0,
Supplementary data
131.2 (Ph), 135.2 (C-5), 169.7 (C-2, CH3CON), 185.1 (CH2COC-3) and
200.4 (C-4), HRMS: calcd for C29H42NO4 468.3108; found 468.3099.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.02.019.
4.3. Synthesis of the complexes 3e4
References and notes
To a solution of the 2a (200 mg, 1.1 mmol) in the minimum
possible amount of ethanol was added Zn(CH3COO)2$2H2O
(120 mg, 0.55 mmol) or Cu(CH3COO)2$H2O (110 mg, 0.55 mmol)
dissolved in the minimum possible amount of ethanol. The
resulting solution was refluxed for 2 h. In the case of the reaction
mixture of 3, the solution was left to cool at rt and the at 0 ꢁC for
24 h to complete the precipitation of yellow transparent crystals.
The crystals were filtrated, washed with ethanol and dried. In the
case of the reaction mixture of 4, the product was precipitated in
the reaction mixture under reflux after 10 min. After 2 h, the
mixture was left to cool at rt and the solid product was filtrated,
washed with ethanol and dried.
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8. (a) Kaufmann, G. F.; Sartorio, R.; Lee, S.; Rogers, C. J.; Meijer, M. M.; Moss, J. A.;
Clapham, B.; Brogan, A. P.; Dickerson, T. J.; Janda, K. D. Proc. Natl. Acad. Sci. U.S.A.
2005, 102, 309; (b) Romano, A. A.; Hahn, T.; Davis, N.; Lowery, C. A.; Struss, A.
4.3.1. [Zn(TAꢀ)2(EtOH)2] (3). Yellow crystals (278 mg, 73%), mp
219e223 ꢁC, lmax (MeOH)/nm 257 (log ε 4.60) and 320 (4.72), lmax
(CHCl3)/nm 346 (4.32), nmax/cmꢀ1 3480 (s), 1725 (s), 1650 (s), 1600,
1450 (s), 1360, 440 (w), dH (300 MHz; DMSO-d6; Me4Si) 1.06 (2.25H,
t, J¼6.0 Hz, CH3CH2OH), 2.41 (3H, s, CH3COC-3), 2.47 (3H, s,
CH3CON), 3.45 (1.5H, quint, J¼6.0 Hz, CH3CH2OH), 4.34 (0.75H, t,
J¼6.0 Hz, CH3CH2OH), 6.84 (1H, s, CH]) and 7.18e7.34 (5H, m, Ph),
dC (75 MHz; DMSO-d6; Me4Si) 18.4 (CH3, EtOH), 26.3 (CH3COC-3),
27.5 (CH3CON), 55.9 (CH2, EtOH), 100.2 (C-3), 116.0 (PhCH]), 127.6,
127.9, 130.0, 130.3, 134.9 (Ph), 134.6 (C-5), 167.8 (C-2), 169.6
(CH3CON), 183.5 (CH3COC-3) and 195.8 (C-4), HRMS: calcd for
€
K.; Janda, K. D.; Bottger, L. H.; Matzanke, B. F.; Carrano, C. J. J. Inorg. Biochem.
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C
30H25N2O8Zn 605.0903; found 605.0841.
ꢁ
Platas, G.; Collado, J.; Gonzalez, A.; de la Cruz, M.; Martin, J.; Kahn, J. N.; Ga-
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4.3.2. Crystal
data. C34H36N2O10Zn,
monoclinic,
P21/c,
¼101.0150(10)ꢁ,
ꢀ
a¼10.5260(9), b¼8.2462(7), c¼19.2086(16) A,
b
cules 2011, 16, 6116.
3
ꢀ
ꢀ
V¼1636.6(2) A , T¼150(2) K,
l¼0.71073 A, Z¼2. 16,162 reflections
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639.
measured, 4068 unique (Rint¼0.0260), wR2¼0.0860 (all data),
R1¼0.0321 (I>2 (I)).
s
4.3.3. [Cu(TAꢀ)2(EtOH)2] (4). Pale green solid (374 mg, 98%), mp
173 ꢁC (dec), lmax (CHCl3)/nm 341 (log ε 4.46) and 642 (2.51), nmax
/
cmꢀ1 3520 (s), 1740 (s), 1690, 1590 (s), 1490 (s), 1370, 490 (w),
HRMS: calcd for C30H25N2O8 604.0908; found 604.0807.
CCDC 965492 and 965493 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
D.M. gratefully acknowledges the Committee of Research of the
National Technical University of Athens for financial support.
21. Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.