Synthesis and properties of new fullerene C60 derivatives, containing acetonide and polyol fragments

Article abstract of DOI:10.1016/j.tet.2014.06.009

New mono- and hexa-methanofullerenes containing different number of acetonide groups are synthesized and characterized. Removing the acetonide protection leads to new chromatographically pure water-soluble polyol methanofullerenes with essentially quantitative yields.

Full text of DOI:10.1016/j.tet.2014.06.009

Accepted Manuscript
Synthesis and properties of new fullerene c derivatives, containing acetonide and
60
polyol fragments
Alina A. Gilmutdinova , Valentina P. Gubskaya , Guzel M. Fazleeva , Shamil K.
Latypov , Tatyana A. Zhelonkina , Dilara R. Sharafutdinova , Ildus A. Nuretdinov ,
Oleg G. Sinyashin
PII:
S0040-4020(14)00855-2
10.1016/j.tet.2014.06.009
TET 25674
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 February 2014
Revised Date: 22 May 2014
Accepted Date: 2 June 2014
Please cite this article as: Gilmutdinova AA, Gubskaya VP, Fazleeva GM, Latypov SK, Zhelonkina
TA, Sharafutdinova DR, Nuretdinov IA, Sinyashin OG, Synthesis and properties of new fullerene
c
derivatives, containing acetonide and polyol fragments, Tetrahedron (2014), doi: 10.1016/
0
6
j.tet.2014.06.009.
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ACCEPTED MANUSCRIPT
SYNTHESIS AND PROPERTIES OF NEW FULLERENE C DERIVATIVES,
6
0
CONTAINING ACETONIDE AND POLYOL FRAGMENTS.
Alina A. Gilmutdinova, Valentina P. Gubskaya, Guzel M. Fazleeva, Shamil K. Latypov,
Tatyana A. Zhelonkina, Dilara R. Sharafutdinova, Ildus A. Nuretdinov, Oleg G. Sinyashin
A.E. Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific centre of RAS,
Arbuzov str. 8, 420088 Kazan, Russian federation
fax (8432)752253 Е-mail: in@iopc.ru
New mono- and hexa-methanofullerenes containing different number of
acetonide groups are synthesised and characterized. Removing the acetonide
protection leads to new chromatographically pure water-soluble polyol
methanofullerenes with essentially quantitative yields.
Keywords: hexa-methanofullerenes, acetonide protection, Bingel-Hirsch reaction, water-soluble
polyol methanofullerenes
Introduction
Prospects of successful application of fullerene С derivatives in biology and medicine are
6
0
substantially defined by possibility of getting their water-soluble forms. A variety of fullerene С60
derivatives, possessing satisfactory solubility in polar solvents, including water-soluble ones has
1
-3
been synthesized. Solubility of the fullerene functional derivatives in water is defined by the
presence of a great number of hydrophilic groups. The overwhelming majority of fullerene water-
soluble derivatives are represented by the compounds containing hydroxyl, carboxyl and amino
4
,5
groups. One of the most water-soluble derivatives of fullerene C60 (240 mg/ml) is the new
malonodiserinolamide polysubstituted methanofullerene obtained by the authors via a new synthetic
4
methodology, which consists of initial protection alcohol groups by ester groups. Subsequent
deprotection leads to a non-ionic, highly water-soluble derivative of C60, however it is necessary to
notice, that it is not an individual compound, but a mixture of tetra-, penta- and hexa-products in the
ratio 15:80:5.
1

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n
Fullerenols (polyhydroxylated fullerenes) С (ОН) , being of simple structure and
6
0
possessing the possibility of further functionalization, also belong to the series of water-soluble
fullerene derivatives. For a long time they were considered as the most appropriate representatives
of water-soluble fullerenes for the study of biological activity. However, depending on the method
of synthesis, fullerenols have various compositions, differing by the number of hydroxyl groups
5
-8
(from 12 to 24), and, respectively, by solubility in water.
Individually isolated tris-
9
-11
dicarboxymethanofullerenes possess good solubility in water and have antiviral effects
.
In an alternative approach, high solubility in water (> 200 mg/ml) is achieved at the expense
of using the phosphorylated groups on the fullerene sphere, obtained from intermediate
12
pentaphosphonic ethers, with their further hydrolysis.
We believe that the approach, based on obtaining fullerene derivatives with protected
hydroxyl groups followed by deprotection seems to be suitable, and suggest to use for these
purposes acetonide protection, which can be easily removed in mild conditions. In this work the
results of research including the development of the methods of synthesis and the study of the
properties of new water-soluble chromatographically-pure fullerene derivatives, containing from 4
to 24 hydroxyl groups per molecule is reported.
Results and discussion
Acetonide derivatives 1, 2, 3 (their yields being 90%, 86%, 61%, respectively) were
obtained by reacting triols (1,1,6-hexanetriol, 1,2,3-propanetriol and 1,2,3-tris-oxymethylethane)
with acetone at the boiling temperature of the former, with catalytic amounts of para-
1
3
toluenesulfonic acid, their structures being proved by spectral methods.
The obtained compounds are precursors for the synthesis of malonate derivatives, containing
acetonide fragments at different distances from the ester group. Malonate derivative 4-6 were then
2

ACCEPTED MANUSCRIPT
obtained by reaction of acetonide derivatives 1-3 with malonyldichloride in the presence of NaH or
Et N in absolute benzene.
3
New malonate fullerene derivatives 7-9, containing acetonide groups, were then synthesized
1
4,
by interaction of fullerene С with initial precursors 4-6 under Bingel-Hirsch reaction conditions.
6
0
1
5
The structures and purities of compounds 7-9 were confirmed by the data from spectroscopic
methods, mass spectrometry, and HPLC. The UV spectra of compounds 7-9 have absorption bands
at 258, 268, 328, and 426 nm typical of virtually all methanofullerenes. The structures of almost all
the title compounds were unambiguously established by a variety of NMR correlation methods.
1
6, 17
Namely, combination of homo- and heteronuclear correlation experiments
(see ESI) allows one
to get the connection between nuclei starting from the ends of addends up to C carbons in most of
61
13
the cases (vide infra e.g. for 7). Then C data analysis allows making final conclusion about the
structure of fullerene derivatives.
3

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1
1
1
13
For example, H- H COSY, H- C HSQC and HMBC connectivity allows discrimination of
addends moiety of 7 (Figure 1) up to C61 (52.3 ppm). Most of the fullerene C60 cage carbons
3
resonate at low fields but there is also one singlet at sp region (δ = 71.6 ppm) that proves the closed
[
6,6]-type of the addend linkage. As a whole, the number of peaks observed for compound 7 in the
2
range 138-146 ppm is due to the 58 sp -carbons of the C60 sphere, consistent with the C symmetry
s
of its molecular structure.
1
13
13
Figure 1. NMR spectra of compounds 7 (a- H, c- C) and 13 (d- C) in CDCl at 303K and
3
structure of 7 (13) with diagnostic HMBC NMR correlations (b).
Having developed the methods for synthesis of new target fullerene derivatives with
protecting groups, we approached the main goal of the present work which is obtaining the
fullerene derivatives containing hydroxyl groups by removing the protecting groups.
Acetonide protection in the synthesized compoundds is easily removed by treating them
with hydrochloric acid (Scheme 2). In a typical experiment, hydrochloric acid (0.27 mmol) was
added to the initial methanofullerene 7 (0.27 mmol), and the reaction mixture was kept in the dark
for 24 hours. At the end of the reaction, the initially wine-red toluene solution of compound 7
4

ACCEPTED MANUSCRIPT
became colorless, and compound 10 precipitated, then it was filtered and washed with toluene and
acetonitrile. The yield of compound 10 was 80%.
Removal of acenonide protection from compounds 8 and 9 similarly resulted in the
formation of compounds 11, 12 (Scheme 1) with yields of 92% and 81%, correspondingly.
Scheme 1.
The solubility of the obtained methanofullerenes 10-12 in polar solvents including water
was studied. Monomethanofullerenes С 10-12 were shown to dissolve well in DMSO/water (1:9)
6
0
solution, but were insoluble in water with various pH values (5-9).
To increase the solubility of the fullerene derivatives in polar solvents (DMSO, ethanol,
water) we synthesized hexa-adducts 13–15 on the basis of malonate precursors 4-6 (Scheme 2)
1
8-21
using the methods described in literature.
5

ACCEPTED MANUSCRIPT
Scheme 2.
For example, to obtain compound 13 we carried out the reaction of fullerene С60 (0.3 g,
0
.42 mmol), bis(2.2-dimethyl-1.3 –dioxalane-4-O-buthyl) malonate (1.73 g, 4.2 mmol), CBr (13.83
4
g, 42 mmol) with DBU (1.27 g, 8.3 mmol) in o-DCB. The reaction mixture was stirred at room
temperature for 72 hours, and purified by column chromatography to yield pure compound 13 (156
mg, yield 11.7 %).
The structure of compounds 13-15 was proved by spectroscopic methods (IR, UV, NMR),
and the composition was proved by MALDI TOF mass-spectrometry. The mass spectrum of
+
compound 13 contains the peak corresponding to the molecular ion [М] 3204.34 (calc. 3204).
Results of NMR experiments strongly support the structures of these hexa-adducts of
[
60]fullerene. First, from variety of NMR correlations the structures of adducts itself up to the C61
1
3
can be unequivocally determined (e.g. for 13 see Figure 1d). In C NMR spectra (Figure 1d) there
are only two signals of equal intensity with δ = 141.1 (24C) and δ = 145.7 ppm (24C)
2
corresponding to sp carbons and only one line (ca. two times less in intensity) with δ = 69.1 ppm
3
(
12C) attributed to sp carbons of the C sphere, and as such it can be concluded that the structure
6
0
of 13 is consistent with high symmetry (Th).
Finally, deprotected hexa-adducts 16-18 were obtained by removing the acetonide protection
from the hexa-adducts 13-15 using the method described earlier for methanofullerenes 10-12.
6

ACCEPTED MANUSCRIPT
1
3
1
The structure of compounds 16-18 was also proved by NMR С and Н spectroscopy, while
their composition was confirmed by mass-spectrometry. The mass-spectrum of compound 17
+
contains the peak corresponding to the [М+Na] = 2243.3 (Fig. 2). The experimental value of the
+
13
isotopic distribution [M+Na] fully corresponds to the theoretical one (insert on Fig.2). The С
NMR spectrum of compound 16 does not contain the signals from the carbons of acetonide
fragment methyl groups (25 and 27 ppm), as well as the NMR proton spectrum does not contain the
signals from the protons of the mentioned groups. Thus compounds 16-18 have the same symmetry
(Th) as the precursors 13-15.
2244.3
100
2244.4
2
243.4
2
245.4
8
0
0
0
0
0
2243.3
2245.3
2246.4
6
4
2
2
247.4
248.4
2
2
241
2243
2245
2247
2249
2251
2253
2
246.3
2
247.3
2248.3
2240
2242
2244
2246
2248
2250
2252
2254
2256
2258
m/z
+
Figure 2. Mass-spectrum for compound 17 [M+Na] , insert –theoretical isotopic distribution
+
[
M+Na] .
The solubility of the obtained polyol methanofullerenes in polar solvents including water was
studied. Methanofullerenes containing 24 hydroxy groups dissolved well not only in DMSO-water
1:9) and ethanol, but also in water with рН= 5, 7 and 9. Hexa-adduct 17, synthesized on the basis
(
of glycerol, demonstrated the best solubility, while increasing the length of the methylene chain in
compound 16 resulted in significant decrease of its solubility in polar solvents and water (Table 1).
7

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Table 1. Solubility of compounds 16-18 in water.
Solubility, mg/ml
DMSO-water
1:9)
рН=5
ascorbic acid/water
рН=9
Tris(oxy-methyl-
amino-methane
рН=7
(physiol. solution)
0,9% NaCl solution
(
Compound
(
2 mg/ml)
(
1 mg/ml)
1
1
1
6
7
8
100 mg/ml
500 mg/ml
250 mg/ml
5 mg/ml
15 mg/ml
35 mg/ml
30 mg/ml
-
10 mg/ml
5 mg/ml
75 mg/ml
75 mg/ml
Conclusion
Thus, the target synthesis of new mono- and hexa-methanofullerenes, containing different numbers
of acetonide groups (from 2 to 12), was realized by the Bingel-Hirsch reaction, their chemical
structures being proved using multiple spectroscopic methods. New chromatographically pure
polyol methanofullerenes, containing 4 and 24 hydroxyl groups, were obtained and their structures
and properties studied. All the hexa-adducts were shown to be well-soluble in various polar solvents
including water. This opens the way to obtaining new derivatives based on fullerenes, containing
various functional groups, responsible for manifestation of biological activity, by reacting the free
hydroxyl groups.
Experimental
HPLC-analysis was performed using Agilent Technologies 1200 Series using UV-detector
with the column with reversed phase C18 (Partisil-5 ODS-3), eluent being toluene/CH CN (volume
3
ratio 1:1). Organic solvents were dried and distilled before use. Fullerene С of 99.9% purity was
60
used (produced by «Fullerene-Center», Nizhny Novgorod). All the chemical reactions were
performed in dry argon atmosphere. UV-spectra were recorded on spectrophotometer Specord M-40
in methylene chloride, IR-spectra were recorded on Fourier-spectrometer «Bruker-Vector 22»
(tablet with КBr). NMR spectra were registered on NMR spectrometer Avance-600 (Bruker) (600
1
13
MHz ( Н) and 150 MHz ( С)) at the temperature 30ºС in CDCl the residual signal from CDCl
3
3
,
(
δ 7.26 ppm and δ 77.0 ppm) being used as an internal standard. The structure of compounds was
Н С
8

ACCEPTED MANUSCRIPT
1
1
established on the basis of a series of 1D and 2D NMR correlation experiments (DEPT, H- H
1
13
1
13
COSY, H- C HSQC, H- C HMBC). MALDI mass spectra were recorded on mass-spectrometer
ULTRAFLEX III (Bruker Daltonik GmbH, Bremen, Germany) in linear regime, with p-nitroaniline
being used as a matrix. Mass-spectra contain the peaks corresponding to the protonated molecular
+
+
+
[
M+H] ion along with frequently present [M+Na] and [M+K] ions.
4
-(2, 2-Dimethyl-1, 3-dioxolane-4-yl)-1-butanol (1)
A solution of 1,2,6-hexanetryol (22.2 g) in distilled acetone (100 ml) with a catalytic amount of p-
toluenesulfonic acid was boiled for 7 h. Then the reaction mixture was cooled and just calcined
potash (100 g) was added. After 12 hours, potash was filtered, and the filtrate was steamed in
vacuum using a water-jet pump. The residue was distilled at T=109-110°С (1 mm Hg). Compound
1
1
1
1
4
1
(19.5 g) with 68% yield was obtained. [Found:C, 62.02; Н, 10.24. С Н О requires: С, 62.07; Н,
9 18 3
-1
0.43%]. IR-spectrum, (liquid film), ν/m : 514, 647, 739, 791, 856, 893, 1058, 1157, 1216, 1248,
1
325, 1370, 1435, 1457, 3424. H NMR (600 MHz, CDCl ):
δ 1.35 (3Н, s, CH ), 1.40 (3Н, s, CH ),
3 3
3
.50-1.65 (6Н, m, СН ), 3.51 (1Н, dd, J= 7.5 Hz, J= 7.5 Hz, СН), 3.65 (2Н, t, J=6.5 Hz, ОСН ),
2
2
1
3
.02 (1Н, dd, J= 7.5 Hz, J= 6.0 Hz, СН), 4.03-4.10 (1Н, m, CH); C NMR (150 MHz, CDCl ):
δ
3
08.65, 75.95, 69.36, 62.52, 33.20, 32.47, 26.87, 25.65, 21.98.
(2, 2-Dimethyl-1, 3-dioxolan-4-yl)-1-methanol (2).
Compound 2 was synthesized analogously to 1. The residue was distilled at T=54-55°С (1 mm Hg).
As a result compound 2 (12.4 g) was obtained with the yield of 39 %. [Found: C, 54.15; Н, 9.64.
-1
С Н О requires: С, 54.3; Н, 9.9%]. IR-spectrum, (liquid film), ν/cm : 516, 567, 653, 792, 844,
6
13
3
1
9
70, 1052, 1074, 1119, 1157, 1214, 1256, 1372, 1457, 3458. H NMR (600 MHz, CDCl ):
δ
1.33
3
(
3Н, s, CH ), 1.40 (3Н, s, СН ), 3.57 (1Н, dd, J= 5.2 Hz, J= 11.9 Hz, СН ), 3.69 (1Н, dd, J= 4.1
3
3
2
Hz, J= 11.9 Hz, СН ), 3.76 (1Н, dd, J= 6.4 Hz, J= 8.1 Hz, СН ), 4.01 (1Н, dd, J= 6.7 Hz, J= 8.1
2
2
13
Hz, СН ), 4.17.4.24 (1H, m, CH); C NMR (150 MHz, CDCl ):
δ 109.33, 76.12, 65.69, 62.95,
2
3
2
6.61, 25.18.
(2, 2, 5-Trimethyl-1, 3-dioxan-5-yl)methanol (3).
Compound 3 was synthesized similarly to 1. Residue was distilled at T= 80°С (1 mm Hg).
Compound 3 (12.8 g) was obtained with 58 % yield. After the distillation the product crystallized,
Тmelt= 29 °С. [Found:C, 59.65; Н, 10.24. С Н О requires: С, 59.92; Н, 10.07 %].IR spectrum,
8
16
3
-1
(
KBr),ν/cm : 521, 562, 679, 731, 790, 829, 912, 933, 989, 1046, 1086, 1153, 1208, 1264, 1349,
1
1
375, 1456, 3441. H NMR (600 MHz, CDCl ):
δ
0.79 (3Н, s, СН ), 1.35 (3Н, s, СН ), 1.40 (3Н, s,
3
3
3
9

ACCEPTED MANUSCRIPT
1
3
СН ), 3.47 (1Н, d, J= 11.7 Hz, СН ), 3.61 (1H, s, CH ), 3.70 (1Н, d, J= 11.7 Hz, СН ); C NMR
3
2
2
2
(150 MHz, CDCl3): δ 98.50, 66.91, 66.22, 35.40, 27.91, 21.14, 18.22.
Bis (2, 2-dimethyl-1, 3-dioxolan 4-O-butyl) malonate (4).
To a suspension of NaH (1.38 g, 0.057 mol) in absolute benzene (100 ml) in the flow of dry argon
at room temperature 2,2–dimethyl-1,3-dioxolane-4-butanol (10 g, 0.057 mol) was added dropwise.
The reaction mixture was stirred at room temperature for 1 h. Having cooled the mixture to a
temperature of 5 °С, malonyldichloride (4.05 g, 0.0287 mol) was slowly added dropwise. The
mixture was stirred for 8 h and then decanted. The organic layer was evaporated in water-jet pump
vacuum. The product was purified by column chromatography (silica gel, eluent: ethylacetate-
hexane (3:1)). After column chromatography a viscous light oil was obtained (R = 0.54). The yield
f
+
of pure product was 44% (5.1 g). Mass-spectrum (MALDI): [M+K] 455.01 C H O IR-spectrum
2
1
36 8.
-1
(
liquid film),ν/cm : 514; 607; 739; 791; 856; 1060; 1097; 1158; 1216; 1331; 1370; 1413; 1458;
1
1
733 (С=О); 2869; 2938; 2985. H NMR (600 MHz, CDCl ):
δ
1.29 (6Н, s, CH ), 1.35 (6Н, s,
3
3
CH ), 1.48-1.73 (12H, m, CH ), 3.33 (2Н, s, СН ), 3.45 (2Н, dd, J= 7.3 Hz, J= 7.3 Hz, СН ), 3.98
3
2
2
2
1
3
(
2Н, dd, J= 7.3 Hz, J= 5.9 Hz, СН ), 4.00-4.06 (2H, m, CH), 4.10 (4H, s, OCH ), C NMR (150
2
2
MHz, CDCl3): δ 166.52, 108.59, 75.64, 69.16, 65.19, 41.37, 32.94, 28.26, 26.75, 25.51, 21.97.
Bis (2, 2-dimethyl-1,3-dioxolane 4-O-methyl) malonate (5).
Compound 5 was synthesized from 2,2–dimethyl-1,3-dioxolane-4-methanol and malonyldichloride
similarly to 4. After column chromatography (silica gel, eluent: ethylacetate-hexane-ethanol
(
2.5:1:0.1)) viscous light oil was obtained with (R = 0.51). Pure product yield was 36% (0.9 g).
f
+
-1
Mass-spectrum (MALDI): [M] 332.92 C H O IR-spectrum (liquid film),ν/cm : 511 , 552, 581,
15
24 8.
6
1
70, 703, 788, 814, 852, 920, 958, 1057, 1096, 1156, 1185, 1205, 1231, 1266, 1316, 1366, 1376,
1
427, 1454, 1539, 1644, 1741, 2930. H NMR (600 MHz, CDCl ):
δ 1.36 (6Н, s, СН ), 1.42 (6Н, s,
3
3
СН ), 3.46 (2Н, s, СН ), 3.75 (2Н, dd, J= 5.8 Hz, J= 8.4 Hz, СН ), 4.07 (2Н, dd, J= 6.7 Hz, J= 8.4
3
2
2
1
3
Hz, СН ), 4.12-4.28 (4H, m, OCH ), 4.28-4.36 (2H, m, CH); C NMR (150 MHz, CDCl ):
δ
2
2
3
1
66.04, 109.90, 73.27, 66.21, 65.68, 41.08, 26.64, 25.29.
Bis (2, 2, 5-trimethyl-1, 3 –dioxane-5-methyl-O-methyl) malonate (6).
To a solution of pentaglyceric semiacetal (1.4 g, 0.0117 mol) and triethylamine (1.18 g, 0.0117
mol) in 50 ml of absolute benzene at 5°С malonyldichloride (0.82 g, 0.0058 mol) was added
1
0

ACCEPTED MANUSCRIPT
dropwise. The reaction mixture was stirred for 8 h. The formed precipitate Et N·HCl was filtered
3
(its weight being 1.3 g), and filtrate was evaporated in the water-jet pump vacuum. The product was
purified by column chromatography on silica gel (eluent was benzene-ethylacetate (5:2)). White
0
crystals with Тmelt 120 С were obtained with the yield 49% (1.1 g). Mass-spectrum (MALDI):
+
+
-1
[
M+Na] 411.9, [M+K] 427.89. C H O IR spectrum (КBr),ν/cm : 507, 557, 582, 672, 705,
19 32 8.
7
35, 827, 911, 924, 956, 1003, 1062, 1090, 1111, 1186, 1205, 1235, 1266, 1318, 1348, 1372, 1395,
1
1
458, 1536, 1646, 1747, 2861, 2950, 2988. H NMR (600 MHz, CDCl ):
δ 0.85 (6Н, s, СН ), 1.39
3
3
(
6Н, s, СН ), 1.43 (6Н, s, СН ), 3.44 (2Н, s, СН ), 3.61 (4Н, d, J= 11.8 Hz, СН ), 3.65 (4Н, d, J=
3
3
2
2
1
3
1
4
1.8 Hz, СН ), 4.26 (4Н, s, ОСН ). C NMR (150 MHz, CDCl ):
δ
166.38, 98.11, 67.86, 66.14,
2
2
3
1.43, 33.60, 27.20, 20.08, 17.60.
6
1-[Bis(2,2-dimethyl-1,3-dioxolane-4-O-butyl) carbonyl]methano[60]fullerene (7)
To a solution of fullerene С (0.3 g, 0.45 mmol) in toluene (200 ml) were sequentially added CBr
4
6
0
(0.208 g, 0.63 mmol), bis(2.2-dimethyl-1.3 –dioxolane-4-O-butyl)malonate (0.26 g, 0.63 mmol) and
DBU (0.095 g, 0.63 mmol). After being stirred for 12 h at room temperature, the reaction mixture
was washed with water (2×20 ml) and concentrated. Compound 7 was isolated by column
chromatography on silica gel with the yield 49% (0.173 g) using the mixture toluene-acetonitrile
+
(40:1). The purity of 7 was confirmed by HPLC methods. Mass-spectrum (MALDI):[M+H]
-
1
134.78 C H O UV-spectrum (CH Cl ), λmax/nm: 327, 428, 490, 696. IR-spectrum, (KBr),ν/cm
81 34 8. 2 2
1
:
526, 552, 579, 609, 638, 671, 705, 738, 789, 812, 854, 995, 1057, 1096, 1156, 1184, 1206, 1232,
1
1
1
7
266, 1369, 1427, 1454, 1538, 1639, 1742, 2327. H NMR (600 MHz, CDCl )
δ
1.34 (6Н, s, СН3),
3
.40 (6Н, s, СН ), 1.53–1.70 (8Н, m, СН ), 1.85-1.94 (4Н, m, СН ), 3.52 (2Н, dd, J= 7.4 Hz, J=
3
2
2
.4 Hz, СН ), 4.04 (2Н, dd, J= 6.0 Hz, J= 7.4 Hz, СН ),, 4.05-4.13 (2H, m, CH), 4.51 (4Н, t, J= 6.6
2
2
1
3
Hz, ОСН ). C NMR (150 MHz, CDCl ):
δ
22.41, 25.75, 27.01, 28.63, 33.20, 52.36, 67.14, 69.41,
2
3
7
1
1.63, 71.88, 108.82, 138.98, 140.98, 141.90, 142.21, 143.01, 143.05, 143.12, 143.90, 144.64,
44.71, 144.91, 145.14, 145.21, 145.29, 163.60 (С=О).
1
1

ACCEPTED MANUSCRIPT
6
1-[Bis(2,2–dimethyl-1,3-dioxolane-4-O-methyl)carbonyl] methano[60]fullerene (8).
Compound 8 was synthesized with the yield 40% relative to the reacted fullerene similarly to
+
compound 7. Mass-spectrum (MALDI): [M+H] 1050.21 C H O . UV-spectrum (CH Cl ),
75
22
8
2
2
-1
λmax/nm: 327, 430, 492, 696. IR-spectrum, (KBr), ν/cm : 526, 552, 581, 670, 703, 788, 814, 852,
9
1
20, 958, 1057, 1096, 1156, 1185, 1205, 1231, 1266, 1316, 1366, 1376, 1427, 1454, 1539, 1644,
1
741, 2930, 3460. H NMR (600 MHz, CDCl )
δ 1.39 (6Н, s, СН ), 1.49 (6Н, s, СН ), 3.91 (2Н,
3 3
3
dd, J= 5.2 Hz, J= 8.8 Hz, СН ), 4.18 (2Н, dd, J= 6.4 Hz, J= 8.8 Hz, СН ), 4.49-4.56 (2H, m, CH),
2
2
1
3
4
6
1
.52 (4Н, s, OСН ). C NMR (150 MHz, CDCl )
δ
25.37 (СН ), 26.84 (СН ), 51.73 (С61), 66.42,
2
3
3
3
3
7.24, 73.14, 73.15, 71.32 (2С-sp ), 110.12 (2С), 139.15, 141.02, 141.88, 141.89, 142.24, 143.03,
43.07, 143.13, 143.92, 144.63, 144.73, 144.97, 145.00, 145.11, 145.24, 145.33, 163.22 (С=О).
6
1-[Bis(2.2.5-trimethyl-1.3-dioxane-5-methyl-O-methyl)carbonyl]methano[60]fullerene (9)
Compound 9 was synthesized with the yield 60% (0.143 g) relative to the reacted fullerene
+
similarly to compound 7. Mass-spectrum (MALDI): [M+H] 1106.07 C H O . UV-spectrum
79
30
8
-1
(
CH Cl ), λ /nm: 326, 429, 491, 697. IR-spectrum, (KBr), ν/cm : 526, 557, 582, 672, 705, 735,
2 2 max
8
1
27, 911, 924, 956, 1003, 1062, 1090, 1111, 1152, 1186, 1205, 1235, 1266, 1318, 1348, 1372,
1
395, 1428, 1458, 1536, 1646, 1747, 2861, 2950, 2988. H NMR (600 MHz, CDCl )
δ 0.96 (6Н,
3
СН ), 1.43 (6Н, s, СН ), 1.47 (6Н, s, СН ), 3.71 (2Н, d, J= 12.0 Hz, СН ), 3.77 (2Н, dd, J= 12.0
3
3
3
2
1
3
Hz, СН ), 4.59 (4Н, s, OСН ). C NMR (150 MHz, CDCl )
δ
17.84, 19.92, 27.4, 52.57 (С61),
2
2
3
3
6
6.16, 71.53 (sp -C), 98.26, 125.30, 128.22, 129.03, 137.85, 139.08, 141.04, 141.92, 142.22,
1
43.04, 143.91, 144.66, 144.69, 144.71, 144.93, 145.08, 145.17, 145.22, 145.30, 163.57 (С=О).
6
1-[Bis(1,2-hexanediol)carbonyl]methano[60]fullerene (10)
To 61-[bis(2,2–dimethyl-1,3-dioxolane-4-O-methyl)carbonyl] methano[60]fullerene 7 (0.019 g,
.167 mmol) in toluene (10 ml) НСl (0.001 ml, 0.167 mmol) was added. The reaction mixture was
0
left in the dark for 24 h. The toluene solution became colourless, sediment precipitated, which was
filtered and washed with toluene, the precipitate weight being 0.016 g, (yield 94%). Mass-spectrum
1
2

ACCEPTED MANUSCRIPT
+
-1
(
MALDI): [M+H] 1055.94 C H O IR-spectrum, ν/cm (KBr): 420, 526, 703, 997, 1024, 1061,
75 26 8.
1
1
096, 1205, 1232, 1267, 1395, 1738, 2855, 2924, 3246, 3384, 3421. H NMR (600 MHz, DMSO-
d ) 1.29-1.52 (8Н, m, CH ), 1.77-1.81 (4Н, m, СН ), 3.25 (4Н, dd, J= 2.1 Hz, J= 5.5 Hz, СН ),
6
2
2
2
1
3
3
2
1
.33-3.48 (2H, m, CH), 4.46 (4Н, t, J= 6.6 Hz, ОСН ). C NMR (150 MHz, DMSO-d )
δ
21.91,
2
6
7.45, 33.01, 52.87, 66.14, 68.89, 71.02, 71.43, 138.94, 140.95, 141.86, 142.18, 142.99, 143.07,
43.84, 144.52, 144.65, 144.69, 144.79, 145.07, 145.13, 145.21, 145.71, 162.83 (С=О).
6
1-[ Bis(1, 2-propanediol) carbonyl)] methano[60]fullerene (11)
Compound 11 was obtained from 8 (0.069g) by the similar method to that of compound 10 with the
+
-1
yield 92% (0.055 g). Mass-spectrum (MALDI): [M+H] 970.01 C H O IR-spectrum, ν/cm
6
9
14 8.
1
(
KBr): 515, 529, 795, 844, 995, 1033, 1076, 1157, 1214, 1257, 1372, 1455, 1659, 1728, 3457. H
NMR (600 MHz, DMSO-d6): 3.35 (2Н, dd, J= 6.0 Hz, J= 6.0 Hz,СН ), 3.84 (2Н, br s, СН), 4.34
δ
2
1
3
(
2H, br s, OCH ), 4.49 (2Н, br s, ОСН ), 5.04 (4H, br s, OH); C NMR (150 MHz, DMSO-d ) δ
2
2
6
2
1
9.65, 52.79, 62.96, 69.11, 69.59, 71.87, 79.74, 139.08, 140.87, 141.86, 142.21, 143.00, 143.06,
43.86, 144.51, 144.65, 144.81, 145.15, 145.23, 145.57, 163.13 (С=О).
6
1-[Bis(2, 3-diol-1-methyl-propyl) carbonyl)] methano[60]fullerene (12)
Compound 12 was obtained from 9 (0.100g) analogously to 10 with the yield 97% (0.09 g). Mass-
+
-1
spectrum (MALDI): [M+H] 1026.90 C H O . IR-spectrum, ν/cm (KBr): 441, 526, 703, 891,
7
3
14
8
1
9
49, 1000, 1046, 1114, 1207, 1233, 1268, 1390, 1427, 1464, 1636, 1741, 3420. H NMR (600
1
3
MHz, DMSO-d6):
MHz, DMSO-d6)
δ 0.89 (6Н, s, СН ), 3.35 (8Н, br s, СН ), 4.31 (4Н, br s, OСН ). C NMR (150
3 2 2
δ
16.95, 53.23, 63.92, 70.19, 72.08, 79.64, 138.93, 140.95, 141.86, 142.18,
1
43.00, 142.98, 143.07, 143.84, 144.52, 144.64, 144.68, 145.15, 145.23, 145.57, 163.47 (С=О).
1
3

ACCEPTED MANUSCRIPT
1
,2:18,36:22,23:27,45:31,32:55,56-{Hexakis([bis(2,2-dimethyl-1.3-dioxolane-4-O-
butyl)carbonyl)]methano}-dodecahydro[60] fullerene (13)
To a solution of С (0.3 g, 0.42 mmol) in O-DCB (20 ml) were added CBr (13.83 g, 42 mmol),
4
6
0
bis(2.2-dimethyl-1.3 –dioxolane-4-O-butyl) malonate (1.73 g, 4.2 mmol) and DBU (1.27 g, 8.3
mmol) at stirring under an argon atmosphere at room temperature. The colour of the reaction
mixture changed immediately from the purple to red. The reaction mixture was stirred for 72 h. The
product 13 was purified by column chromatography on silica gel at eluating with the mixture
+
hexane-ethylacetate with the yield 12% (0.156 g). Mass-spectrum (MALDI): [M+H] : 3204.34
-1
C H O . IR spectrum (КBr),ν/cm : 529, 540, 673, 856, 995, 1061, 1160, 1219, 1264, 1456,
1
86 204 48
1
1
644, 1746, 2286, 2868, 2936, 2984, 3468. H NMR (600 MHz, CDCl ) δ 1.33 (36H, s, CH ), 1.38
3 3
(
36H, s, CH ), 1.40-1.65 (48H, m, CH ), 1.71-1.75 (24H, m, CH ) 3.48 (12H, dd, J= 6.4 Hz, J= 6.8
3 2 2
Hz, CH ), 4.00 (12H, dd, J= 6.4 Hz, J= 7.2 Hz, CH ), 4.02-4.07 (12H, m, CH), 4.26 (24H, t, J= 6.4
2
2
13
Hz, OCH ); C NMR (150 MHz, CDCl )
δ
22.45, 26.02, 27.05, 28.62, 33.21, 45.56, 66.89, 69.95,
2
3
3
2
2
7
5.84 (sp ), 108.82, 141.05 (sp ), 146.1 (sp ), 164.00.
1
,2:18,36:22,23:27,45:31,32:55,56-{Hexakis[bis(2,2–dimethyl-1,3-dioxolane-4-O-
methyl)carbonyl)]methano}-dodecahydro[60] fullerene (14)
Compound 14 was obtained by the method similar to that for compound 13 with the yield 20%
+
-1
(
0.181 g). Mass-spectrum (MALDI): [MH] 2701.20 C H O IR spectrum (КBr),ν/cm : 523,
150 132 48.
1
6
65, 715, 795, 841, 936, 998, 1056, 1158, 1213, 1263, 1376, 1455, 1645, 1749, 2986. H NMR
(600 MHz, CDCl3)
δ
1.36 (36Н, s, СН ), 1.43 (36Н, s, СН ), 3.76 (12Н, dd, J= 5.4 Hz, J= 5.4 Hz,
3
3
CН ), 4.07 (12Н, dd, J= 6.7 Hz, J= 7.2 Hz, CН ), 4.30 (24Н, s, ОСН ), 4.31-4.39 (12Н, m, СН);
2
2
2
1
3
3
C NMR (150 MHz, CDCl3)
δ
25.24, 26.70, 44.89 (6С, С ), 60.30, 66.38, 66.41, 68.92 (sp ),
61
2
2
7
1
2.91, 109.91, 140.88 (sp ), 145.84 (sp ), 163.16 (С=О).
,2:18,36:22,23:27,45:31,32:55,56-{Hexakis[bis(2.2.5-trimethyl-1.3-dioxane-5-methyl-O-methyl)
carbonyl)]methano}-dodecahydro[60] fullerene (15)
1
4

ACCEPTED MANUSCRIPT
Compound 15 was obtained by a method similar to that for compound 13 with the yield 28% (0.156
+
g).
-spectrum (КBr),ν/cm-1: 523, 673,
Mass-spectrum (MALDI): [MH] 3038.3 С174
H
180
O48. IR
1
7
14, 828, 913, 935, 1002, 1043, 1090, 1155, 1206, 1264, 1375, 1459, 1748 (С=О), 2960. H NMR
(
600 MHz, CDCl3) δ 0.81 (36Н, s, СН ), 1.37 (36Н, s, СН ), 1.41 (36Н, s, СН ), 3.55 (24Н, d, J =
3 3 3
1
3
1
1
2 Hz, СН ), 3.62 (24Н, d, J = 12 Hz, СН ) 4.35 (24Н, s, ОСН ); C NMR (150 MHz, CDCl ) δ
2 2 2 3
3
7.63, 20.08, 27.08, 30.79, 33.59, 40.37, 45.44 (6С, С ), 66.00, 69.10 (sp ), 69.33, 98.00, 141.07
61
2
2
(
sp ), 145.65 (sp ), 163.47 (С=О).
1
,2:18,36:22,23:27,45:31,32:55,56-{Hexakis[(bis(1.2-hexanediol)carbonyl)]methano}-
dodecahydro[60]fullerene (16)
To a solution of compound 13 (0.022 g, 0.0069 mmol) in toluene (10 ml) НСl (0.002 ml, 0.082
mmol) was added. The reaction mixture was left for 24 h in a dark. The toluene mixture became
colorless, the sediment precipitated, which was filtered and washed with toluene. The product yield
+
was 95% (0.018 g). Mass-spectrum (MALDI): [MH ] 2724.80 C H O IR spectrum (KBr),
1
50 156 48.
-1
ν/cm : 533, 672, 715, 924, 972, 1077, 1221, 1265, 1459, 1741 (С=О), 2438, 2783, 2866, 2934,
1
3
369 (ОН). H NMR (600 MHz, DMSO-d )
δ
1.15-1.35 (24H, m, CH ), 1.41 (24H, br s, CH ), 1.61
6
2
2
(
24H, br s, CH ), 3.22 (24 H, d, J= 5.1 Hz, CH , 3.36 (12Н, br s, CH), 4.26 (24H, t, J = 5.9 Hz,
2
2
1
3
OCH ); C NMR (150 MHz, DMSO-d )
δ
21.19, 28.78, 32.38, 45.52 (6С, С ), 65.80, 66.43,
2
6
61
3
2
2
6
7.08, 68.95, 70.91 (sp ), 140.50 (sp ), 145.01 (sp ), 162.53 (С=О).
1
,2:18,36:22,23:27,45:31,32:55,56-{Hexakis[(bis(1.2-propanediol)carbonyl)]methano}-
dodecahydro[60]fullerene (17).
Compound 17 was obtained from 14 (0.041g) analogously to 16 with the yield of 94% (0.031g).
+
-1
Mass-spectrum (MALDI): [MH] 2220.30 C H O IR spectrum (КBr), ν/cm : 472, 525, 565,
1
14 84 48.
6
00, 708, 756, 840, 977, 1017, 1050, 1095, 1161, 1187, 1262, 1367, 1436, 1543, 1653, 1742 (С=О),
1
2
926, 3423 (ОН). H NMR (600 MHz, DMSO-d ):
δ 3.27-3.45 (24H, m, CH ), 3.73 (12Н, br s,
2
6
1
5

ACCEPTED MANUSCRIPT
13
CH), 4.15-4.33 (24H, m, OCH ); C NMR (150 MHz, DMSO-d ):
δ 45.41-45.53 (6С, С ), 59.27,
61
2
6
3
2
2
6
2.31, 63.04, 68.43, 68.94, 72.42 (sp ), 140.62 (sp ), 145.03 (sp ), 162.72 (С=О).
1
,2:18,36:22,23:27,45:31,32:55,56-{Hexakis[(bis(2.3-diol-1-methyl-propyl) carbonyl)] methano}-
dodecahydro[60]fullerene (18)
Compound 18 was obtained analogously to compound 16 from 15 (0.030 g) with the yield of 99%
+
-1
(
0.025 g). Mass-spectrum (MALDI): [MH] 2556.30 C H O . IR spectrum (КBr, ν, cm ): 527,
138 132 48.
5
42, 598, 714, 826, 941, 1040, 1126, 1224, 1372, 1396, 1466, 1736 (С=О), 2880, 2932, 3359 (ОН).
1
H NMR (600 MHz, DMSO-d6):
δ = 0.75 (36Н, br s, СН ), 3.25 (48Н, br s, СН ), 4. 12 (24Н, br s,
3 2
1
3
OСН ); C NMR (150 MHz, DMSO-d )
δ
17.63, 30.79, 33.59, 40.37, 45.44 (6С, С ), 66.00, 69.10
2
6
61
3
2
2
(
sp ), 69.33, 98.00, 141.07 (sp ), 145.65 (sp ), 163.47 (С=О).
Financial support of the Program for Fundamental research of the Presidium of RAS 24P and
RFBR (grant № 12-03-97084 р-Povolzhie-a) is highly appreciated.
The study of the structure of compounds is performed in the department of Federal
share spectral-and-analytical centre for physical-chemical research of structure, properties
and composition of substances and materials (Joint use centre SAC) and Federal Joint Use
centre for physical-chemical research of substances and materials (FJUC PCR) (state
contracts of the Ministry of education and science of RF № 02.451.11.7036 и
0
2.451.11.7019).
References
1
.
.
Nakamura, E., Isobe, H. Acc. Chem. Res. 2003, 36, 807-815.
2
Piotrovskii, L.B., Kiselev, O. I. in Fullerenes in biology// North-west department of the
Russian Academy of medicine – St. Petersburg.: “Rostok” Publishers, 2006, ch.4, pp. 92-112.
3.
Cataldo, F., Da Ros, T. in Medicinal Chemistry and Pharmacological Potential of Fullerenes
and Carbon Nanotubes. Springer, 2008.
1
6

ACCEPTED MANUSCRIPT
4.
Wharton, T., Kini, V. U., Mortis, R.A., Wilson, L.J. Tetrahedron Lett. 2001, 42, 5159–5162.
5
.
.
Chiang, L. Y. U.S. Patent 5648523, 1995.
6
Li, J., Takeuchi, A., Ozawa, M., Li, X., Saigo, K., Kitazawa, K. J. Chem. Soc., Сhem.
Commun. 1993, 1784-1788.
7
.
.
.
Chiang, L.Y., Yang, W.L., Swirczewski, J.W., Soled, S., Cameron, S., J. Org. Chem. 1994. 59,
3
960-3968.
Chiang, L.Y., Bhonsle, J.B., Wang, L., Shu, S.F., Chang, T.M., Hwu, J.R. Tetrahedron 1996,
2, 4663-4672.
Lamparth, I., Hirsch, A. J. Chem. Soc. Chem. Commun. 1994, 1727-1728.
8
5
9
1
0. Dugan, L.L., Turetsky, D.M., Du, C., Lobner, D., Wheeler, M., Almli, C.R., Shen, C.K.F.,
Luh, T.-Y., Choi, D.W., Lin, T.-S. Proc. Natl. Acad. Sci. USA, 1997, 94, 9434-9439.
1. Lin, Y.-L., Lei, H.-Y., Luh, T.-Y., Chou, C.-K., Liu, H.-S. Virology, 2000, 275, 258-262.
2. Yurkova, A.A., Khakina, E.A., Troyanov, S.I., Chernyak, A., Shmygleva, L., Peregudov, A.S.,
Martynenko, V.M., Dobrovolskiy, Yu.A., Troshin, P.A. Chem. Commun. 2012, 48, 8916-8918.
3. Lacey, C.J., Loew, L.M. J. Org. Chem. 1983, 48, 5214-5221.
1
1
1
1
1
1
4. Bingel, C. Chem.Ber. 1993, 126, 1957.
5. Camps, X., Hirsch, A. J. Chem. Soc., Perkin Trans. I, 1997, 1595.
6. Derome, A. E., Modern NMR Techniques for Chemistry Research; Pergamon: Cambridge,
1
988.
17. Atta-ur-Rahman, One and Two Dimensional NMR Spectroscopy; Elsevier: Amsterdam, 1989.
18. Hirsch, A., Vostrowsky, O. Eur. J. Org. Chem. 2001, 829-848.
19. Li, H., Haque, A., Kitaygorodskiy, A., Meziany, M. J., Torres-Castillo, M., Sun, Ya. P. Org.
Lett. 2006, 8, 5641-5643.
2
0. Hormann, F., Donaubauer, W., Hampel, F., Hirsch, A. Eur. J. 2012, 18, 3329-3337.
1. Hormann, F., Hirsch, A. Chem.-Eur. J. 2013, 19, 3188-3197.
2
1
7

ACCEPTED MANUSCRIPT
Synthesis and properties of new fullerene C derivatives, containing acetonide and
6
0
polyol fragments.
Alina A. Gilmutdinova, Valentina P. Gubskaya, Guzel M. Fazleeva, Shamil K. Latypov,
Tatyana A. Zhelonkina, Dilara R. Sharafutdinova, Ildus A. Nuretdinov, Oleg G. Sinyashin
A new approach for synthesis of chromatographically pure water-soluble
polyol methanofullerenes with almost quantitative yields has been developed.
RO
OR
'RO
OR'
OR
OR'
O
O
O
O
O
O
O
O
OR
OR'
O
O
HCl
O
O
OR'
OR'
O
O
O
O
O
O
RO
-CH
OR
'RO
OR'
CH
3
CH
3
R = -CH
2
,
2
,
-
CH
2
R' = -CH
2
,
-CH2
,
-
CH2
O
O
O
O
HO OH
HO OH
O
O
H
O
O
H
1
8

ACCEPTED MANUSCRIPT
Supporting Information
Synthesis and properties of new fullerene C derivatives, containing acetonide and polyol fragments.
6
0
Alina A. Gilmutdinova, Valentina P. Gubskaya, Guzel M. Fazleeva, Shamil K. Latypov,
Tatyana A. Zhelonkina, Dilara R. Sharafutdinova, Ildus A. Nuretdinov, Oleg G. Sinyashin
Table of contents
pages
1
13
Figure S1. 1D H, C and DEPT spectra in CDCl of 7 (T = 303K).
4
5
3
1
1
Figure S2. 2D H- H COSY spectrum in CDCl3 of 7 (T = 303K).
1
13
Figure S3. 2D H- C HSQC spectrum in CDCl of 7 (T = 303K).
6
3
1
13
Figure S4. 2D H- C HMBC spectrum in CDCl of 7 (T = 303K).
7
3
1
13
Figure S5. 1D H, C and DEPT spectra in CDCl of 8 (T = 303K).
8
3
1
13
Figure S6. 1D H, C and DEPT spectra in CDCl of 9 (T = 303K).
9
3
1
13
Figure S7. 1D H, C and DEPT spectra in DMSO of 10 (T = 303K).
10
11
12
13
1
1
Figure S8. 2D H- H COSY spectrum in DMSO of 10 (T = 303K).
1
13
Figure S9. 2D H- C HSQC spectrum in DMSO of 10 (T = 303K).
1
13
Figure S10. 2D H- C HMBC spectrum in DMSO of 10 (T = 303K).
1
13
Figure S11. 1D H, C and DEPT spectra in DMSO of 11 (T = 303K).
14
1

ACCEPTED MANUSCRIPT
1
1
Figure S12. 2D H- H COSY spectrum in DMSO of 11 (T = 303K).
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
1
13
Figure S13. 2D H- C HSQC spectrum in DMSO of 11 (T = 303K).
1
13
Figure S14. 2D H- C HMBC spectrum in DMSO of 11 (T = 303K).
1
13
Figure S15. 1D H, C and DEPT spectra in DMSO of 12 (T = 303K).
1
1
Figure S16. 2D H- H COSY spectrum in DMSO of 12 (T = 303K).
1
13
Figure S17. 2D H- C HSQC spectrum in DMSO of 12 (T = 303K).
1
13
Figure S18. 2D H- C HMBC spectrum in DMSO of 12 (T = 303K).
1
13
Figure S19. 1D H, C and DEPT spectra in CDCl of 13 (T = 303K).
3
1
1
Figure S20. 2D H- H COSY spectrum in CDCl of 13 (T = 303K).
3
1
13
Figure S21. 2D H- C HSQC spectrum in CDCl of 13 (T = 303K).
3
1
13
Figure S22. 2D H- C HMBC spectrum in CDCl of 13 (T = 303K).
3
1
13
Figure S23. 1D H, C and DEPT spectra in CDCl of 14 (T = 303K).
3
1
1
Figure S24. 2D H- H COSY spectrum in CDCl of 14 (T = 303K).
3
1
13
Figure S25. 2D H- C HSQC spectrum in CDCl of 14 (T = 303K).
3
1
13
Figure S26. 2D H- C HMBC spectrum in CDCl of 14 (T = 303K).
3
1
13
Figure S27. 1D H, C and DEPT spectra in CDCl of 15 (T = 303K).
3
1
1
Figure S28. 2D H- H COSY spectrum in CDCl of 15 (T = 303K).
3
1
13
Figure S29. 2D H- C HSQC spectrum in CDCl of 15 (T = 303K).
3
1
13
Figure S30. 2D H- C HMBC spectrum in CDCl of 15 (T = 303K).
3
1
13
Figure S31. 1D H, C and DEPT spectra in CDCl of 16 (T = 303K).
3
1
1
Figure S32. 2D H- H COSY spectrum in CDCl of 16 (T = 303K).
3
1
13
Figure S33. 2D H- C HSQC spectrum in CDCl of 16 (T = 303K).
3
1
13
Figure S34. 2D H- C HMBC spectrum in CDCl of 16 (T = 303K).
37
3
2

ACCEPTED MANUSCRIPT
1
13
Figure S35. 1D H, C and DEPT spectra in CDCl of 17 (T = 303K).
38
39
40
41
42
43
44
45
3
1
1
Figure S36. 2D H- H COSY spectrum in CDCl of 17 (T = 303K).
3
1
13
Figure S37. 2D H- C HSQC spectrum in CDCl of 17 (T = 303K).
3
1
13
Figure S38. 2D H- C HMBC spectrum in CDCl of 17 (T = 303K).
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Figure S39. 1D H, C and DEPT spectra in CDCl of 18 (T = 303K).
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Figure S40. 2D H- H COSY spectrum in CDCl of 18 (T = 303K).
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Figure S41. 2D H- C HSQC spectrum in CDCl of 18 (T = 303K).
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Figure S42. 2D H- C HMBC spectrum in CDCl of 18 (T = 303K).
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NMR Spectroscopy. All NMR experiments were performed with a Bruker AVANCE-600 and AVANCE-400 spectrometers. Frequencies are 600.13
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MHz in H NMR and 150.90 MHz in C NMR experiments for AVANCE600; 399.93 МHz in Н NMR and 100.57 МHz in С NMR for
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AVANCE400. NMR experiments were carried out using standard Bruker pulse programs. The pulse widths were 7 µs (90°) and 12 µs (90°) for H and
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C, respectively. Typically 16K and 64K data points were collected for one-dimensional proton and carbon spectra, respectively. 2D experiments
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parameters were as follows. For H– H correlations (COSY): relaxation delay 1.5 s, data matrix 1K x 2K (256 experiments to 0.5K, zero filling in F1,
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K in F2), 2 transients in each experiment. For H- C correlations (HSQC): optimized for J = 145 Hz, relaxation delay 2.5 s, data matrix 0.5K x 2K
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(
256 experiments to 0.5K, zero filling in F1, 2K in F2), 16 transients in each experiment. For H- C long range correlations (HMBC): optimized for J
8 Hz, relaxation delay 2.5 s, data matrix 0.5K x 2K (256 experiments to 0.5K, zero filling in F1, 2K in F2), 48 transients in each experiment. All 2D
spectra were weighted with sine-bell squared and shifted (π/2 in both dimensions) window functions, and processed with the Bruker software package.
=
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Figure S1. 1D H, C and DEPT spectra in CDCl of 7 (T = 303K).
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Figure S2. 2D H- H COSY spectrum in CDCl3 of 7 (T = 303K).
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Figure S3. 2D H- C HSQC spectrum in CDCl of 7 (T = 303K).
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Figure S4. 2D H- C HMBC spectrum in CDCl of 7 (T = 303K).
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Figure S51D H and C spectra in CDCl of 8 (T = 303K).
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Figure S6. 1D H and C spectra in CDCl of 9 (T = 303K).
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Figure S7. 1D H, C and DEPT spectra in DMSO of 10 (T = 303K).
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Figure S8. 2D H- H COSY spectrum in DMSO of 10 (T = 303K).
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