Synthesis of 2,6-disubstituted tetrahydroazulene derivatives

Article abstract of DOI:10.3762/bjoc.8.77

Synthesis of hydroazulene derivatives has been carried out through a ring-enlargement route by using carbene adduct intermediates. The protocol can be applied for the construction of functionalized hydroazulene skeletons as key components of many natural products as well as the core system of novel liquid-crystalline materials.

Full text of DOI:10.3762/bjoc.8.77

Synthesis of 2,6-disubstituted tetrahydroazulene
derivatives
Zakir Hussain*1,2, Henning Hopf1, Khurshid Ayub2 and S. Holger Eichhorn3
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 693–698.
1Institut für Organische Chemie, Technische Universität
Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany; Fax:
+49 5313915388, 2Department of Chemistry, COMSATS Institute of
Information Technology (CIIT), University Road, Abbottabad 22060,
KPK, Pakistan; Fax: +92 (992) 383441 and 3Department of Chemistry
and Biochemistry, University of Windsor, 401 Sunset Avenue, Essex
Hall, Windsor, ON Canada N9B 3P4, Fax: +1 (519) 973-7064
doi:10.3762/bjoc.8.77
Received: 16 December 2011
Accepted: 17 April 2012
Published: 04 May 2012
This article is part of the Thematic Series "Progress in liquid crystal
chemistry II".
Email:
Zakir Hussain* - chem63@yahoo.com
Guest Editor: S. Laschat
* Corresponding author
© 2012 Hussain et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
carbene addition; hydroazulenes; liquid crystals; ring expansion
Abstract
Synthesis of hydroazulene derivatives has been carried out through a ring-enlargement route by using carbene adduct intermediates.
The protocol can be applied for the construction of functionalized hydroazulene skeletons as key components of many natural prod-
ucts as well as the core system of novel liquid-crystalline materials.
Introduction
Hydroazulene skeletons provide the basic ring systems of employed [10,11] the method reported by Keehn et al. [12]
natural products, such as guaianolide sesquiterpenes [1,2] and using Birch reduced indanes for the synthesis of 2,6-disubsti-
the so-called furanether B series [3,4]. The stereoselective syn- tuted perhydroazulene systems as core elements of novel liquid-
thesis of trans-hydroazulene derivatives by a tandem Michael/ crystalline (LC) materials.
intramolecular Wittig approach was reported previously [5].
Recently, a new synthetic method for the construction of a As far as mesogenic compounds are concerned, there is still a
hydroazulene skeleton by a [5 + 2]cycloaddition reaction was growing need for more new derivatives to be synthesised and
also developed [6]. Additionally, there have been many reports tested for features desirable for novel displays, which include,
on the synthesis of 2,6-disubstituted azulenes [7,8]. In 1951, the but are not limited to, lower driving voltages, lower power
ring expansion of indanes was reported for the synthesis of such consumption and faster response times. In contrast to the core
systems, but it delivered only very low yields [9]. We recently system presently used in most nematic LC materials, our new
693

Beilstein J. Org. Chem. 2012, 8, 693–698.
core based on perhydroazulenes showed [13], e.g., improved The complete characterization of intermediates 2 and 3 and
properties regarding phase-transition temperatures. Therefore, carbene adduct 4 was carried out by NMR and related analyt-
due to its potential use as a subsystem of many natural products, ical techniques, similar to previous reports [18], while the 3D
as well as as the core moiety for novel LC materials, further structure of 4 was further established based on the X-ray data of
investigation on perhydroazulene-based substrates and syn- its derivative 6 [20].
thetic intermediates is desirable.
It is important to note that the addition resulted in higher yields
Results and Discussion
when the length of time used for the addition of the ethyl diazo-
The synthesis of various intermediates and the final hydroazu- acetate was extended, which was again similar to our earlier
lene derivatives 9 and 10 is described in this section. 2-Indan- investigations [10]. The formation of only one major isomer (4)
carboxylic acid (1) [14] was reduced under Birch conditions in this case could be due to the greater steric hindrance for
[15] to 4,7-dihydro-2-indancarboxylic acid (2) as the kineti- carbene addition to the inner carbon–carbon double bond, in
cally controlled product. In order to carry out carbene additions spite of the fact that the central olefinic double bond is more
to the obtained 1,4-cyclohexadiene system, esterification [16] of electron-rich and, hence, in principle more susceptible to such
2 was carried out in a one-pot procedure in DMF at 40 °C with additions. In order to elucidate the configuration of 4, ester
1,1'-carbonyldiimidazole, tert-butyl alcohol and DBU to afford cleavage with formic acid was carried out resulting in the acid 6
ester 3 in quantitative yield. The ester 3 was then subjected to as a colorless solid, which was recrystallized from hexane and
carbene addition by treatment with ethyl diazoacetate in the dichloromethane to afford single crystals suitable for X-ray
presence of a copper catalyst [17] in THF under reflux. The analysis. The X-ray data [20] showed that the central, six-
carbene adduct 4 was obtained as the major product, as a color- membered ring is almost planar but is slightly folded about the
less oil in acceptable yields (55–60%, Scheme 1). In addition to axis C(2)···C(6); the five-membered ring is essentially planar.
4, we were able to isolate the side product 5 in ca. 10% yield. The two larger rings are approximately coplanar, but the three-
The formation of carbene adduct 4 from 2-indancarboxylic acid and six-membered rings form an interplanar angle of 78.4(1)°.
(1) can also be followed from the previous work [18]. The atoms of the ester side chain are coplanar and this plane
Evidently, in the formation of the adduct, the carbene attacks forms a dihedral angle of 78.73(4)° with the central ring. In the
the central double bond of the substrate.
crystal, the molecules form hydrogen-bonded dimers across
inversion centers. Furthermore, a triplet in the 1H NMR spec-
trum at δ = 1.54 ppm with a coupling constant of 4.2 Hz
between the H-atoms at the cyclopropyl ring, indicates an anti-
relation between the ethoxycarbonyl group and the cyclo-
hexene ring.
The subsequent step comprised the ring opening of 4 to furnish
the cycloheptatrienes 7 and 8. The carbene adduct 4 was first
treated with bromine leading to the formation of the corres-
ponding dibromide, which was then followed by elimination
with triethylamine to afford triethylamine hydrobromide along-
side the formation of a norcaradiene intermediate in situ, which
was transformed into the 2,6-disubstituted tetrahydroazulene 7
as a viscous oil. It is important to note that tetrahydroazulenes,
in contrast to perhydroazulenes, are not very resistant towards
dehydrogenation (oxidation) and, when kept at room tempera-
Scheme 1: Preparation of carbene adducts 4 [18] and 5.
It is worth mentioning that in our earlier work on similar com- ture for a few days, form the corresponding azulenes (giving a
pounds [19], we isolated at least two isomers of 4 (with the bluish color).
methine hydrogen atom at the five-membered ring being present
at either the α or β position). In our earlier work [10], carbene Similar to our earlier investigations [10], various isomers could
addition to similar compound(s) was found to give a mixture of be formed through the rearrangement of double bonds in the
stereoisomers. However, in the present case, we were only able seven-membered ring of 7. However, through the NMR data of
to isolate 4 as a single stereoisomer. Furthermore, the proce- 7, we saw the formation of an isomer with double bonds at the
dure for the synthesis of compounds 4 and 5 is essentially the ring junction as a major isomer. Formation of one major isomer
same as described previously for analogous compounds [10]. under the given conditions could be explained through the
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Beilstein J. Org. Chem. 2012, 8, 693–698.
hydrogen shifts of cycloheptatrienes by the so-called The cycloheptatriene unit of 9 adopts, in sterically relaxed
Berson–Willcott rearrangement [21]. We assume that bro- systems, a boat-like conformation, whereas its planar form
mination (Br2) and dehydrobromination (Et3N) of 4 resulted in represents the transition state of the thermal boat-inversion
the formation of an intermediate, which converted to 7 through process. Additionally, since 8 and 9 possess a center of chirality
thermal disrotatory electrocyclic ring opening and a base- at C(2), there are two different boat conformations of the cyclo-
catalyzed prototropic shift. The ester 7 underwent acid- heptatriene unit possible, namely those in which C(4) is on the
catalyzed hydrolysis (formic acid) to afford 8 as a solid, which same or on the opposite side with respect to the substituent at
on recrystallization resulted in single crystals suitable for X-ray C(2). The 1H NMR spectrum (400 MHz, CDCl3) of 9 displays
analysis (Scheme 2).
diastereotopic (syn and anti to the ester group) H-atoms at C(4),
indicating that the ring-inversion process is still slow at the
temperature of the measurement, but the observed dd signals
already show some line broadening.
Structure elucidation of compounds 9 and 10 was carried out by
1D and 2D NMR spectroscopy. Most 13C-signals could be
assigned through HMQC analysis. For quaternary carbons,
analysis of HMBC data was sufficient to complete the assign-
ment. In the 1H NMR spectrum of compound 9, the H-atom
(HA or Hα) at C(1) is located in the deshielding region of the
carbonyl function and, hence, resonates slightly downfield
(from its geminal H-atom, HB) at δ = 2.94 ppm, together with
the H-atoms at C(3), whereas HB (Hβ) itself resonates at δ =
2.92 ppm. Furthermore, the H-atom at C(2), being geminal to a
strongly deshielding carboxylate group, gives a multiplet at δ =
Scheme 2: Preparation of the cycloheptatrienes 7 and 8 [18,20].
The structural analysis of 8 revealed [22] an azulene frame- 3.49 ppm. Additionally, H-atoms at C(14) and C(18) show a
work that is partially hydrogenated to a cyclopentane subunit in doublet at δ = 7.22 ppm (J = 8.7 Hz), which is acceptable for
places where molecules are slightly disordered in the lattice. such protons after considering the effect of cyano and carboxyl-
These molecules represent the slightly torsionally distorted ate groups on the respective positions of the aromatic ring. The
enantiomers of 8. At this stage we did not find any hydrogen doublet at δ = 7.65 ppm (J = 8.7 Hz), integrated for two
atom at position 6; however, additional H-atoms at C(4) and protons, was assigned to the H-atoms at C(15) and C(17). The
C(8), each with only 50% occupancy, were found. Acid 8 was most differentiated signals were identified for H-atoms at C(4)
further condensed [23] with p-cyanophenol in the presence of giving two distinct dd at δ = 2.50 ppm (J = 7.1, 13.4 Hz) and at
SOCl2 and DMAP in dichloromethane to obtain the corres- δ = 2.65 ppm (J = 7.5, 13.5 Hz). These values seem very rea-
ponding ester. The GC analysis of the product mixture indi- sonable considering the envelope form of the seven-membered
cated the presence of two isomers (ratio 3:1), which were later ring, in which C(4) extends out of the plane of the ring thereby
separated through reversed-phase HPLC (MeOH/H2O 3:1) and allowing the remaining six carbon atoms to enhance the
characterized as derivatives 9 and 10 (Scheme 3).
delocalization. This six-carbon system in turns generates a ring
current similar to benzene, though less pronounced, allowing
HA to resonate in the deshielding region (δ = 2.65 ppm) and HB
in the shielding region (δ = 2.50 ppm). The H-atoms at posi-
tions C(5) and C(8) of the seven-membered ring (being almost
in identical electronic environments), give a broad multiplet at
δ = 6.52 ppm. However, a pronounced doublet at δ = 6.96 ppm
(J = 11.2 Hz) is assigned for the hydrogen atom at position C(7)
considering the effect of the nearby carboxylate group and
several sp2-hybridized carbon atoms in its immediate vicinity
on both sides.
In the case of compound 10, due to shifting of the double bonds,
the single H-atom at C(4) becomes olefinic (conjugated)
thereby resonating together with C(8); it displays a doublet at
Scheme 3: Preparation of derivatives 9 and 10.
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Beilstein J. Org. Chem. 2012, 8, 693–698.
δ = 5.47 ppm (J = 9.2 Hz). Similarly, the H-atoms at C(5) and Mass spectra were recorded by using a Finnigan MAT 8430
C(7) give dd at δ = 6.22 ppm (J = 5.6, 9.1 Hz). The single spectrometer using the electron-ionization method (EI, 70 eV).
proton at C(6) provides a triplet at δ = 2.73 ppm (J = 5.6 Hz). Synthesis and analytical data of compounds 2–4 and 6 can be
However, the exact stereochemistry at C(6) could not be estab- found in the literature [18].
lished in the present case.
Ethyl 2-tert-butoxycarbonyl-2,3,4,7-tetrahydro-1H-3a,7a-
Finally, we investigated compounds 9 and 10 under a polar- methanoinden-8-carboxylate (5): Compound 5 was obtained
izing microscope for their textural features, and DSC experi- as a highly viscous, colorless oil in 10% yield during the syn-
ments were carried out to determine the phase-transition thesis of carbene adduct 4 as given in the literature [18]. Rf 0.41
temperatures. In the case of 9, the first melting-point peak in the (SiO2; hexane/CH2Cl2 1:1); IR (film): 2900 (m, CH-stretch),
DSC never recovered, but a very broad transition at 5 °C was 1695 and 1700 (s, C=O), 1340, 1250, 1133 (m) cm−1; 1H NMR
observed subsequently indicating the possibility of a very (200.1 MHz, CDCl3) δ 1.21 (t, 3J = 7.1 Hz, H-C(11)),
exothermic process on cooling to −40 °C. Furthermore, after the 1.31–1.40 (s, C(CH3)3), 1.55–1.68 (m, CH2(1), CH2(3)), 1.62
first melting the sample was an isotropic liquid down to 0 °C. (br s, H-C(8)), 2.31 (br s, CH2(4), CH2(7)), 2.78–2.81 (m,
The first melting showed complex behavior over a temperature H-C(2)), 4.08 (q, J = 7.1 Hz, CH2(10)), 5.49 ppm (br s, H-C(5),
range of 30 °C, and areas with Schlieren-like textures were H-C(6)); 13C NMR (50.3 MHz, CDCl3) δ 14.1 (q, C(11)), 27.80
present but were never recovered or reproduced. In the case of (q, C(CH3)3), 29.41 (d, C(8)), 31.23 (t, C(4), C(7)), 34.31 (s,
compound 10, the same behavior was observed. As we C(3a), C(7a)), 38.23 (d, C(2)), 42.68 (d, C(1), C(3)), 61.01 (t,
mentioned earlier, tetrahydroazulenes, in contrast to perhy- C(10)), 80.12 (s, C(CH3)3), 125.60 (d, C(5), C(6)), 171.84,
droazulenes, are not very resistant against dehydrogenation 172.01 (s, C(9), C(12)); EIMS m/z: 306 (8, M+), 249 (57, [M −
(oxidation), and when kept at room temperature for a few days, C4H9]+), 205 (80, [M − C5H9O2]+), 132 (100, [205 −
they form the corresponding azulenes. Such an unusual behav- C3H5O2]+); HRMS (m/z): [M]+ calcd for C18H26O4,
ior of compounds 9 and 10 can easily be attributed to their oxi- 306.183109; found, 306.183123 + 1.1 ppm.
dation. Additionally, our earlier investigations on similar com-
pounds [10,13] showed that fully hydrogenated derivatives 6-Ethyl-tetrahydroazulene-2-carboxylate (8): To a stirred
show pronounced mesogenic behavior.
solution of 4 (3.06 g, 0.01 mol) in CHCl3 (100 mL), a solution
of Br2 (0.6 mL, 0.01 mol) in CHCl3 (5 mL) was added drop-
wise at 0 °C. When the addition was complete, triethylamine
Experimental
Thin-layer chromatography was performed by using precoated (6.91 mL, 49.71 mmol) was added. Triethylamine hydrobro-
plastic plates, PolyGram Sil G/UV254. Column chromatog- mide began to form immediately. The mixture was heated under
raphy was performed on silica gel 60 (70–230 mesh) from reflux for 18 h. After cooling, the hydrobromide was filtered
Merck (Darmstadt). HPLC analysis was carried out on a system off. The filtrate was evaporated and the resulting oil partitioned
consisting of Shimadzu (Duisburg, Germany), Gilson 305 between benzene and dilute aqueous acid (HCl). The benzene
pumps, a Shimadzu SPD-M10AV UV–vis detector, and a frac- layer was washed with water, dried with MgSO4 and filtered,
tion collector. In the GC system, a Hewlett-Packard 6890 with a and the solvent was removed. The reaction mixture was filtered
flame-ionization-detection (FID) system was used. All chro- through a small column of silica gel, eluting with pentane and
matograms were processed by ColaChrom software (Version dichloromethane (1:2). After evaporation of the solvent the
8.1) developed by MPI für Kohlenforschung, Mülheim, crude product 7 was obtained as a viscous bluish oil (2.6 g,
Germany. All organic solvents used in the study were HPLC 85%). The preparation of compound 7 is analogous to that
grade and were purchased from Baker GmbH, Germany. The described in [10]. The crude intermediate 7 was not purified
argon gas used was of high-purity grade. IR spectra were further and was subjected to hydrolysis directly: A solution of 7
recorded using a Nicolet 320 FT-IR and a Bruker Tensor 27 (1.0 g, 3.29 mmol) in formic acid (100 mL) was stirred at rt for
spectrometer. Samples were prepared either as KBr pellets or as 15 h. The solvent was removed under reduced pressure and the
thin films. 1H and 13C NMR spectra were recorded on the crude product was recrystallized from hexane and dichloro-
following spectrometers: Bruker AC-200, 1H NMR methane to give 0.71 g (85%) of 8 as slightly bluish needles. Rf
(200.1 MHz), 13C NMR (50.3 MHz); Bruker DRX-400, 0.35 (SiO2; EtOAc/CH2Cl2 1:5); IR (film): 2913 (m, CH,
1H NMR (400.1 MHz), 13C NMR (100.6 MHz). Chemical stretch.), 1712, 1718 (s, C=O), 1320, 1150 (m) cm−1; 1H NMR
shifts (δ) are expressed in parts per million (ppm) downfield (200.1 MHz, CDCl3) δ 1.29 (t, 3J = 7.1 Hz, CH3(12)),
from tetramethylsilane or by using the residual nondeuterated 2.80–3.27 (m, CH2(1), CH2(3), H-C(2)), 4.18 (q, J = 7.1 Hz,
solvent as the internal standard (CDCl3: 1H, δ = 7.26 ppm; 13C, CH2(11)), 2.60–2.75/5.48–6.69 ppm (2 × m, 5 H, seven-
δ = 77.00 ppm). Coupling constants are expressed in hertz. membered ring-H); 13C NMR (50.3 MHz, CDCl3) δ 14.21 (q,
696

Beilstein J. Org. Chem. 2012, 8, 693–698.
C(12)), 27.50 (t), 37.53 (t), 39.39 (t), 41.97 (d), 60.79 (d, (s, C=O), 1342, 1223, 1165 (m) cm−1; 1H NMR (400.1 MHz,
C(11)), 117.87 (d), 124.60 (d), 126.61 (d), 130.61 (d), 133.99 CDCl3) δ 1.29 (t, 3J = 7.1 Hz, CH3(11)), 2.73 (t, J = 5.6 Hz,
(s), 132.70 (s), 166.81, 181.41 ppm (s, C(9), C(10)); EIMS m/z: H-C(6)), 3.16 (m, CH2(1), CH2(3)), 3.42 (m, H-C(2)), 4.25 (q, J
248 (19, M+), 219 (59, [M − C2H5]+), 203 (18, [M − = 7.1 Hz, CH2(10)), 5.47 (d, J = 9.2 Hz, H-C(4), H-C(8)), 6.22
C2H5O]+), 175 (72, [M − C3H5O2]+), 129 (100, [175 − (dd, J = 5.6, 9.1 Hz, H-C(5), H-C(7)), 7.23 (d, J = 8.8 Hz,
HCO2H]+); HRMS (m/z): [M]+ calcd for C14H16O4, H-C(15), H-C(17)), 7.69 (d, J = 8.8 Hz, H-C(14), H-C(18));
248.104859; found, 248.104835 + 0.96 ppm.
13C NMR (100.6 MHz, CDCl3) δ 14.0 (q, C(11)), 39.24 (t,
C(1), C(3)), 40.95 (d, C(6)), 45.0 (d, C(2)), 60.9 (t, C(10)),
1,2,3,4-Tetrahydroazulene-2,6-dicarboxylic acid 2-(4-cyano- 109.56 (s, C(19)), 117.94 (s, C(16)), 118.08 (2 × d, C(5), C(7)),
phenyl) ester 6-ethyl ester (9): Thionyl chloride (0.021 mL, 122.39 (2 × d, C(4), C(8)), 124.28 (2 × d, C(15), C(17)), 133.45
0.28 mmol) was added to a solution of 4-(N,N- (2 × d, C(14), C(18)), 139.44 (2 × s, C(3a), C(8a)), 153.83 (s,
dimethylamino)pyridine (34 mg, 0.27 mmol) in dichlorometh- C(13)), 172.50 (s, C(9)), 172.80 ppm (s, C(12)); EIMS 349 (26,
ane (5 mL) at −20 °C. Acid 8 (70 mg, 0.28 mmol) was added [M+]), 320 (100, [M − C2H5]+), 304 (16, [M − C2H5O]+), 276
and the resulting solution was stirred for 1 h. Then, 4-(N,N-di- (16, [M − C3H5O2]+), 203 (57, [M − C8H4O2N]+); HRMS
methylamino)pyridine (34 mg, 0.27 mmol) and the (m/z): [M + Na]+ calcd for C21H19NO4Na, 372.120362; found,
p-cyanophenol (31 mg, 0.30 mmol) in dichloromethane were 372.120630 + 1.05 ppm.
added and the stirring was continued for another 1 h. The mix-
ture was washed with water (5 mL), and the organic layer was
Supporting Information
separated and dried with sodium sulfate to give a crude mixture
of 9 and 10 (75 mg, 72%). The product mixture was filtered
Supporting Information File 1
through a small column of silica gel, eluting with pentane and
dichloromethane (1:2), to remove impurities, and was further
separated through reversed-phase HPLC. The analytical HPLC
indicated the presence of both isomers 9 and 10 in a 3:1 ratio.
For preparative HPLC, the sample was dissolved in MeOH/
CH2Cl2, and MeOH/H2O 75:25 (v/v) was used as a mobile
phase. Compound 9 was isolated in 97% purity (tR 4.40 min),
while 10 was obtained in 94% purity (tR 4.98). Rf 0.32 (SiO2;
hexane/CH2Cl2 1:1); mp 83–84 °C; IR (film): 2931 (m CH,
stretch), 1705 and 1714s (C=O), 1311, 1230, 1122 (m) cm−1;
1H NMR (400.1 MHz, CDCl3) δ 1.29 (t, 3J = 7.1 Hz, CH3(11)),
2.50 (dd, J = 7.1, 13.4 Hz, Hβ(4)), 2.65 (dd, J = 7.5, 13.5 Hz,
Hα(4)), 2.92 (m, CH2(3), Hβ(1)), 2.94 (dd, J = 6.8, 17.4 Hz,
Hα(1)), 3.49 (m, H-C(2)), 4.21 (q, J = 7.1 Hz, CH2(10)), 6.52
(br. m, H-C(5), H-C(8)), 6.96 (d, J = 11.2 Hz, H-C(7)), 7.22 (d,
J = 8.7 Hz, H-C(14), H-C(18)), 7.65 ppm (d, J = 8.7 Hz,
H-C(15), H-C(17)); 13C NMR (100.6 MHz, CDCl3) δ 14.01 (q,
C(11)), 27.26 (t, C(4)), 37.43 (t, C(3)), 39.63 (t, C(1)), 42.01 (d,
C(5)), 60.63 (t, C(10)), 109.49 (s, C(19)), 117.94 (s, C(16)),
122.39 (d, C(2)), 126.74 (d, C(8)), 128.50 (2 × d, C(15), (17)),
130.47 (d, C(7)), 130.81 (s, C(3a), 132.27 (s, C(8a)), 133.50
(2 × d, C(14), C(18)), 133.61 (s, C(6)), 153.83 (s, C(13)),
166.52 (s, C(9)), 172.76 ppm (s, C(12)); EIMS m/z: 349 (27,
[M+]), 320 (100, [M − C2H5]+), 304 (17, [M − C2H5O]+), 276
(18, [M − C3H5O2]+), 203 (56, [M − C8H4O2N]+); HRMS
(m/z): [M + Na]+ calcd for C21H19NO4Na, 372.120362; found,
372.120629 + 0.72 ppm.
DSC-data of isomers 9 and 10.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-77-S1.pdf]
Acknowledgements
Z. H. thanks Prof. Dr. Wolfgang Gärtner at the Max-Planck
Institute for Bioinorganic Chemistry, Mülheim (Germany) for
his support in purification and characterization all new
substances in the present study.
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