Ferrocenyltriazoles from 3β,28-Diacylbetulin: Synthesis and Cytotoxic Activity

Article abstract of DOI:10.1134/S1070428019110083

The reaction of 30-bromo-3β,28-diacylbetulin with sodium azide afforded 30-azido-3β,28-diacyloxylup-20(29)-enes. The products were subjected to a CuI/TMEDA-catalyzed click reaction with ethynylferrocene to obtain the corresponding ferrocene-betulin conjug

Full text of DOI:10.1134/S1070428019110083

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 11, pp. 1690–1697. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 11, pp. 1722–1729.
Ferrocenyltriazoles from 3β,28-Diacylbetulin:
Synthesis and Cytotoxic Activity
V. A. Glushkova,b,*, D. A. Shemyakinab, N. K. Zhukovab, L. V. Pavlogradskayaa,
M. V. Dmitrievb, D. V. Eroshenkoa, A. R. Galeevb, and I. G. Mokrushinb
a Institute of Technical Chemistry, Perm Federal Research Centre, Ural Branch, Russian Academy of Sciences,
ul. Akademika Koroleva 3, Perm, 614013 Russia
*e-mail: glusha55@gmail.com
b Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
Received April 25, 2019; revised September 19, 2019; accepted September 20, 2019
Abstract—The reaction of 30-bromo-3β,28-diacylbetulin with sodium azide afforded 30-azido-3β,28-
diacyloxylup-20(29)-enes. The products were subjected to a CuI/TMEDA-catalyzed click reaction with
ethynylferrocene to obtain the corresponding ferrocene−betulin conjugates with a 1,2,3-triazole linker.
Keywords: betulin, ferrocene, 1,2,3-triazole
DOI: 10.1134/S1070428019110083
Over the past years the click synthesis of triazoles
from mono-, di-, and triterpenoids has gained wide
popularity [1–3]. Most reactions of triterpenoids
involve the functional groups bound with the C2 [4, 5],
С3 [6–8], and С28 atoms of the triterpene core [9–15],
as well as bound both to С3 and С28 [16]. Only a few
examples of the triazole synthesis from lupane deri-
vatives, where the functional group bound to С30 was
involved, are available in the literature [17, 18]. On the
other hand, today there is continuing search for
biologically active compounds, including those with
anticancer effects, among ferrocene derivatives [19–
25]. Previously, we obtained by click chemistry con-
jugates of betulonic acid with ferrocene, bound by a
1,2,3-triazole bridge at C28 [26, 27].
in the presence of 4-(dimethylamino)pyridine. The
structure of dipropionyl derivative 1b was confirmed
by X-ray diffraction (XRD) analysis (Fig. 1).
The radical allylic bromination of diacylbetulins
1a–1c was performed with bromosuccinimide in a
mixture of CCl4 and CH2Cl2 under reflux in the pre-
sence of AIBN by a known procedure (Scheme 1) [35].
30-Bromo derivative of diacetylbetulin 2а is
described in [36]. By recrystallization of bromide 2а
from petroleum ether was obtained its single crystal.
The XRD analysis confirmed the structure of
compound 2а, but the Br atom could not be localized
exactly because of the poor quality of the crystal.
The present study was undertaken as a continuation
of our research into the synthesis of ferrocene-
substituted triterpenoids. The aim of this work was to
obtain ferrocene conjugates with a 1,2,3-triazole linker
at C30 from 3β, 28-diacyl derivatives of betulin and to
study their cytotoxic activity.
As the starting substrates we took 3β,28-
diacetylbetulin (1a) [28–30], 3β,28-dipropionylbetulin
(1b) [31, 32], and 3β,28-dibenzoylbetulin (1c) [33,
34]. Compounds 1b and 1c were synthesized by
treating technical betulin with an acylating agent
(propionic anhydride or benzoyl chloride) in pyridine
Fig. 1. General view of a molecule of compound 1b by the
XRD data (thermal ellipsoids are drawn at a 30%
probability level).
1690

FERROCENYLTRIAZOLES FROM 3β,28-DIACYLBETULIN: SYNTHESIS
1691
Scheme 1.
Br
R
O
O
R
O
O
NBS, AIBN
CCl4_CH2Cl2,
reflux, 5_7 h
O
O
R
O
R
O
1a_1c
2a_2c, 53_62%
1, 2, R = Me (a), R = Et (b), R = Ph (c).
1
The Н NMR spectra of 3β,28-dipropionyl- (2b)
and 3β,28-dibenziylbetulins (2c) no longer show the
СН3С= at signals at 1.67–1.74 ppm, observed in the
spectrum of starting diacylbetulins 1a–1c, but contain
a new singlet at 3.97–4.03 ppm assignable to the
BrCH2 protons; the Н29 proton signals of compounds
2b and 2c are shifted downfield compared to the
respective signals of 1b and 1c: 5.02 and 5.12 ppm
(2b) against 4.58 and 4.67 ppm (1b) and 5.10 and
5.19 ppm (2c) against 4.65 and 4.76 ppm (1c).
that this system showed a good performance in our
previous studies [26, 27].
1
According to the Н NMR spectra, the reaction
formed a single triazole isomer, specifically 4-subs-
tituted 1,2,3-triazole 4a–4c (yields 37–63%), as evi-
denced by the observation of a characteristic signal of
the triazole С5Н proton at 7.39–7.43 ppm and the
corresponding С5 signal at 119 ppm in the 13C NMR
spectra, which is consistent with published data for
1,4-disubstituted 1,2,3-triazoles [17, 37].
The reactions of bromides 2a–2c with sodium azide
in DMSO gave azido derivatives 3a–3с (yields 54–
62%). Evidence for the formation of these products is
provided by the presence in their IR spectra of a band
at 2099–2105 cm–1 characteristic of the azido group.
Azides 3a–3с were subjected to a Cu-catalyzed [3+2]-
cycloaddition reaction (click chemistry) with ethynyl-
ferrocene (Scheme 2). As the catalyst we used CuI
(10 mol %) doped with TMEDA, in view of the fact
The structure of compounds 4b and 4c was
1
confirmed by 2D correlation H–13С NMR spectros-
copy (HMBC). The HMBC spectrum of compound 4c
clearly demonstrates long-range coupling between the
Н2С30 protons with С5', С20, and С29 (Fig. 2).
The in vitro cytotoxicity of the compounds was
assessed against MS (melanoma), A549 (lung carci-
noma) and RD (rhabdomyosarcoma) human tumor cell
Scheme 2.
Fc
N3
N
N
N
R
Fc
O
CuI (10 mol %)
TMEDA
R
O
NaN3
O
2a_2c
O
DMSO, 60°C
3_5 h
toluene, 80°C,
4_6 h
O
O
R
O
R
O
3a_3c, 33_62%
4a_4c, 37_63%
3, 4, R = Me (a), R = Et (b), R = Ph (c); Fc = ferrocene.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

GLUSHKOV et al.
1692
ppm
Fig. 2. Fragment HMBC NMR spectrum of compound 4c.
lines. To this end, solutions of the test compounds in
DMSO (1.6–100 μM) were added to cell monolayers
formed in the wells of a 96-well plate. The wells with
0.1% DMSO were used as a control, and Camp-
tothecin, as a reference drug.
spectra. Elemental analysis was performed on a Vario
EL cube CHNOS analyzer. The melting points were
determined on a PTP apparatus. The specific rotations
were measured on a Perkin–Elmer 341 polarimeter in
chemical grade chloroform containing 0.5% of ethanol
and are reported in 10–1·deg g–1 cm2. Column chroma-
tography was performed on Silicagel 60 (Alfa Aesar,
0.060–0.2 mm, 70–230 mesh), eluent petroleum ether
(40–70°С)–ethyl acetate. The reaction progress was
monored by TLC on Sorbfil plates, eluent petroleum
ether (40–70°С)–ethyl acetate, 7 : 3; the spots were
visualized by treatment with 20% H2SO4 followed by
heating. Ethynylferrocene was synthesized as desc-
ribed in [39]. Sodium azide, Cu(I) iodide, 4-(dimethyl-
amino)pyridine, benzoyl chloride, and N-bromosuccin-
imide were purchased from Alfa Aesar, propionic
anhydride, from Aldrich, and pure grade petroleum
ether and chemical grade ethyl acetate, propan-2-ol,
DMSO, and pyridine, from Russian producers.
Cell viability was assessed after 72-h incubation
after adding the MTT solution by measuring the
optical density of the formed formazane at 544 nm on
a Labtech FLUOstar OPTIMA BMG spectrophoto-
meter. The IC50 values were calculated from the dose–
effect plots. It was found that the cytotoxic activity
increases in the order 4b < 4c < 4a (Table 1). Com-
pound 4a showed moderate activity against the MS
line (IC50 = 48.71±3.55 μM).
EXPERIMENTAL
The IR spectra were recorded on a Bruker
VERTEX 80v FTIR spectrometer in thin films
obtained by evaporation of chloroform solutions of the
X-ray diffraction analysis of compound 1b.
Compound 1b crystallizes in a centrosymmetric space
group of the rhombic system. The bond lengths and
bond angles are normal values. All six-membered rings
are in a chair conformation. The five-membered ring
has an envelope conformation with the C17 atom
1
analyzed compounds. The Н and 13С NMR spectra
were measured in CDCl3 on a Bruker Avance III HD
400 spectrometer (400 and 100 MHz, respectively),
1
using as internal references HMDS for the Н NMR
spectra and CDCl3 (δC 77.0 ppm) for the 13С NMR
Table 1. Cyctotoxicity of diacylbetulin−ferrocene conjugates 4а–4c
IC50, µM
Compound no.
MS
RD
>200
A549
131.00±7.54
>200
4a
48.71±3.55
>200
4b
4c
>200
128.0±9.54
0.77±0.34
>200
107.3±1.53
1.31±0.03
Camptothecin
1.72±0.37
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

FERROCENYLTRIAZOLES FROM 3β,28-DIACYLBETULIN: SYNTHESIS
1693
deviating from the plane formed by the other 4 atoms
by 0.64 Å. No specific shortened contacts in the crystal
were found.
technical betulin was added. After 12-h stirring at
room temperature, the reaction mixture was poured
into 500 mL of cold water, and the precipitate that
formed was filtered off, washed with 5% acetic acid
and water, dried in air, and recrystallized from ethanol
to obtain 10.7 g (72%) of compound 1c as colorless
fine crystals, mp 159–161°С (139–140°С [33]; color-
less oil [34]). Rf 0.65. The 1Н and 13С NMR spectra are
consistent with those reported in [34].
The XRD analysis was performed on an Xcalibur
Ruby diffractometer with a ССD detector by a stan-
dard procedure (MoKα radiation, 295(2) K, ω scans,
scan steps 1°). Empirical absorption corrections were
applied SCALE3 ABSPACK [40]. Compound 1b
(C36H58O4, M 554.82), rhombic crystal, space group
P212121, a 12.875(3) Å, b 15.786(4) Å, c 16.289(4) Å,
V 3310.6(13) Å3, Z 4, dcalc 1.113 g/cm3, μ 0.070 mm–1.
The structure was solved using Superflip [41] and
refined by full-matrix least squares on F2 with ani-
sotropic temperature factors for all non-hydrogen
factors using SHELXL [42] with OLEX2 graphical
user interface [43]. Hydrogen atoms were refined
riding on their carrier atoms. Final refinement para-
meters: R1 0.0652, wR2 0.1517 [for 4063 reflections
with I > 2σ(I)], R1 0.1113, wR2 0.1796 (on all 6689
unique reflections), S 1.022. The results of the XRD ana-
lysis of compound 1b are deposited at the Cambridge
Crystallographic Data Center (www.ccdc.cam.ac.uk/
data_request/cif), CCDC 1910975.
30-Bromolup-20(29)-en-3β,28-diyldipropionate
(2b). A mixture of 1.88 g (3.4 mmol) of compound 1b
and 0.6 g (3.4 mmol) of N-bromosuccinimide in 80 mL
of СCl4 containing 100 mg of AIBN (recrystallized
from ethanol) was heated under reflux for 5 h, cooled,
washed with cold water to separate succinimide, dried
over MgSO4, the solvent was removed by distillation,
and the residue was subjected to column chroma-
tography. Yield 1.15 g (53%), colorless crystals, mp
150–151°С, Rf 0.61, [α]D24 +2.4 (CHCl3, c 1). IR spec-
trum, cm–1: 2944, 2874, 1733, 1462, 1390, 1356, 1275,
1
1188, 1082, 1015, 968, 757. Н NMR spectrum, δ,
ppm: 0.83 s (6H, 2Me), 0.84 s (3H, Me), 0.98 s (3H,
Me), 1.03 s (3H, Me), 1.13 t (3Н, СН3, 3J 7.2 Hz), 1.15 t
(3Н, СН3, 3J 7.2 Hz), 2.33 q [2Н, С(О)СН2, 3J 7.2 Hz],
3
2
2.34 q [2Н, С(О)СН2, J 7.2 Hz], 3.83 d (1Н, Н28, J
10.8 Hz), 3.97 s (2Н, СН2Br), 4.27 d (1Н, Н28, 2J 10.8 Hz),
4.46 m (1Н, Н3), 5.02 s (1Н, Н29), 5.12 s (1Н, Н29). 13С
NMR spectrum, δ, ppm: 9.12, 9.22, 14.66, 15.98,
16.04, 16.42, 18.08, 20.86, 23.61, 26.90, 26.99, 27.59,
27.86, 27.94, 29.57, 29.82, 32.45, 34.11, 34.24, 37.00,
37.41, 37.78, 38.33, 40.89, 42.61, 43.31, 46.43, 50.19,
50.27, 55.32, 62.22, 80.22 (С3), 113.18 (С20), 150.77
(С29), 174.01 (С=О), 174.41 (С=О). Found, %: C
68.53; H 10.19; Br 12.47. C36H57BrO4. Calculated, %:
C 68.23; H 9.07; Br 12.31.
Lup-20(29)-ene-3β,28-diyldipropionate (1b). A so-
lution of 20 g (45 mmol) of technical betulin (purity ~
90%), 17.5 mL (136 mmol, 17.7 g) of propionoc
anhydride, and 0.55 g (4.5 mmol, 10 mol %) of 4-(di-
methylamino)pyridine in 180 mL of pyridine was
heated on a water bath for 1 h and left to stand
overnight. The reaction mixture was then poured into a
mixture of 300 mL of water, 200 mL of conc. HCl, and
100 g of crushed ice, the mixture was stirred, and the
tar that formed was dissolved in 300 mL of
dichloromethane. The solution was washed with water,
5% HCl, saturated NaHCO3 and NaCl, dried over
MgSO4, the solvent was removed by distillation, and
the residue was crystallized from 250 mL of propan-2-
ol with a little of water to obtain 10.08 g (48%) of
compound 1b as nearly colorless prisms. The ana-
lytical sample was obtained by recrystallization from
petroleum ether–ethyl acetate, coarse transparent
prisms, mp 162–164°С (149°С [31]; 163.6°С [32]). Rf
30-Bromolup-20(29)-ene-3β,28-diyldibenzoate
(2c). A mixture of 4.28 g (7.41 mmol) of compound 1c
and 1.38 g (7.41 mmol) of N-bromosuccinimide in a
mixture of 200 mL СCl4 and 50 mL of CH2Cl2,
containing 200 mg of AIBN was heated under reflux
for 5 h, cooled, washed with water to separate succin-
imide, dried over MgSO4, the solvent was removed by
distillation, and the residue was subjected to column
chromatography (eluent petroleum ether–ethyl acetate,
20 : 1). Yield 3.09 g (57%), colorless crystals, mp 148–
151°С, Rf 0.63, [α]D24 +26.2 (CHCl3, s 1). IR spectrum,
cm–1: 2947, 2878, 1716 (С=О), 1451, 1390, 1315,
1274, 1215, 1176, 1114, 1070, 1026, 971, 757, 711. 1Н
NMR spectrum, δ, ppm: 0.89 s (3H, Me), 0.90 s (3H,
Me), 0.98 s (3H, Me), 1.01 s (3H, Me), 1.08 s (3Н,
1
13
0.63. The Н and С NMR spectra are consistent with
those reported in [31].
Lup-20(29)-ene-3β,28-diyldibenzoate (1c). Ben-
zoyl chloride, 5.34 mL (6.47 g, 46 mmol), and 3.05 g
(25 mmol) of 4-(dimethylamino)pyridine were added
to 80 mL of pyridine and 80 mL of dioxane. The
mixture was stirred, after which 10 g (23 mmol) of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

GLUSHKOV et al.
Me), 2.51 m (1Н, Н19), 3.98 s (2Н, BrССН2), 4.09 d
1694
(c 1, CHCl3), Rf 0.57. IR spectrum, cm–1: 2947, 2872,
2099 (N3), 1715 (С=О), 1451, 1391, 1347, 1316, 1274,
1216, 1176, 1115, 1070, 1026, 972, 757, 711. 1Н NMR
spectrum, δ, ppm (the multipletes of the lupane ring
СН2 and СН protons are not shown): 0.95 s (3H, Me),
0.96 s (3H, Me), 1.04 s (3H, Me), 1.07 s (3H, Me),
1.13 s (3H, Me), 2.50 m (1Н, Н19), 3.82 s (2Н,
CН2N3), 4.12 d (1Н, Н28, 2J 12.0 Hz), 4.57 d (1Н, Н28,
2J 12.0 Hz), 4.75 m (1Н, Н3), 5.03 s (1H, H29), 5.08 s
(1H, H29), 7.45 m (4Нarom), 7.56 m (2Нarom), 8.07 m
(4Нarom). 13С NMR spectrum, δ, ppm: 14.32, 15.63,
16.27, 17.72, 20.51, 22.10, 23.27, 26.39, 26.67, 27.63,
28.54, 29.56, 30.83, 33.73, 34.04, 36.68, 37.11, 37.65,
37.98, 40.46, 42.31, 43.68, 46.33, 49.45, 49.82, 62.47,
81.05, 111.22, 127.78, 127.87, 129.02, 129.05, 129.97,
130.59, 132.13, 132.38, 148.12, 165.75 (С=О), 166.35
(С=О). Found, %: C 76.25; H 8.28; N 5.96.
C44H57N3O4. Calculated, %: C 76.38; H 8.30; N
6.07.
2
2
(1Н, Н28, J 12.0 Hz), 4.53 d (1Н, Н28, J 12.0 Hz),
4.71 m (1Н, Н3), 5.05 s (1Н, Н29), 5.14 s (1Н, Н29),
7.41 m (4Нarom), 7.51 m (2Нarom), 8.02 m (4Нarom). 13С
NMR spectrum, δ, ppm: 14.81, 16.12, 16.14, 16.75,
18.19, 20.98, 23.74, 25.25, 27.02, 27.15, 28.10, 30.11,
32.60, 34.20, 34.51, 37.61, 38.19, 38.44, 41.01, 42.79,
43.47, 46.79, 50.30, 50.43, 55.47, 63.12, 81.52,
113.34, 128.26, 128.40, 129.49, 129.54, 130.44,
131.03, 132.62, 132.85, 150.84, 166.22 (С=О), 166.83
(С=О). Found, %: C 72.17; H 8.02; Br 10.79.
C44H57BrO4. Calculated, %: C 72.41; H 7.87; Br
10.95.
30-Azidolup-20(29)-ene-3β,28-diyldiacetate (3a)
is described in [17].
30-Azidolup-20(29)-en-3β,28-diyldipropionate
(3b). Solium azide, 120 mg (1.90 mmol), was added to
a solution of 300 mg (0.476 mmol) of bromide 2b in
20 mL of DMSO, and the mixture was stirred at 60–
70°С for 5 h. After cooling, the mixture was poured
into a mixture of 150 mL of water and 100 g of ice,
acidified with 10 mL of conc. HCl, the precipitate that
formed was filtered off, washed with water, dried in
air, and the residue was subjected to column
chromatography on silica gel (eluent petroleum ether–
ethyl acetate, 10 : 1). Yield 175 mg (62%), pale yellow
powder, mp 129–130°С, [α]D25 +7.0 (c 0.5, СHCl3), Rf
0.55. IR spectrum, cm–1: 2944, 2874, 2099 (N3), 1734
(С=О), 1462, 1390, 1356, 1275, 1216, 1187, 1082,
Click reaction (general procedure). Compound
3a–3c (or 9a–9c), 1 mmol, and 210 mg (1 mmol) of
ethynylferrocene [39] were dissolved in 20 mL of
toluene, after which 19.2 mg (0.1 mmol, 10 mol %) of
CuI and 3 droplets of TMEDA were added to the
solution, and the reaction mixture was stirred at 80°С
for 3–4 h. The reaction progress was monitored by
TLC. Toluene was removed by distillation, and the
residue was subjected to column chromatography on
silica gel in petroleum ether–ethyl acetate (the fraction
of ethyl acetate in the eluent was gradually increased
from 0 to 20%).
1
1016, 970, 887, 806, 757. Н NMR spectrum, δ, ppm:
0.83 s (6H, 2Me), 0.84 s (3H, Me), 0.97 s (3H, Me),
30-(4-Ferrocenyl[1,2,3]triazol-1-yl)lup-20(29)-
ene-3β,28-diyldiacetate (4a). Yield 484 mg (63%),
yellow foam, mp 143–146°С, Rf 0.21. IR spectrum, ν,
cm–1: 3094, 2947, 2873, 1731 (С=О), 1463, 1391,
1.03 s (3H, Me), 1.13 t (3Н, СН3, 3J 7.2 Hz), 1.15 t (3Н,
3
3
СН3, J 7.2 Hz), 2.33 q [2Н, С(О)СН2, J 7.2 Hz],
2.34 q [2Н, С(О)СН2, J 7.2 Hz], 3.75 s (2Н СН2N3),
3
3.83 d (1Н, Н28, J 12.0 Hz), 4.26 d (1Н, Н28, J
12.0 Hz), 4.46 m (1Н, Н3), 4.95 s (1Н, Н29), 5.00 s
(1Н, Н29). 13С NMR spectrum, δ, ppm: 9.17, 9.27,
14.71, 16.03, 16.10, 16.49, 18.14, 20.91, 23.68, 26.81,
27.04, 27.67, 27.93, 28.03, 29.83, 31.23, 34.16, 34.33,
37.07, 37.43, 37.87, 38.39, 40.95, 42.68, 44.17, 46.17,
46.49, 49.88, 50.24, 55.39, 62.20, 80.48, 111.61,
148.49, 174.36, 174.67. Found, %: C 72.55; H 7.04; N
6.87. C36H57N3O4. Calculated, %: C 72.57; H 9.64; N
7.05.
2
2
1
1366, 1247, 1106, 1032, 979, 756. Н NMR spectrum,
δ, ppm: 0.83 s (3H, Me), 0.84 s (6H, 2Me), 0.98 s (3H,
Me), 1.01 s (3H, Me), 2.03 s [3H, CH3C(O)], 2.04 s
2
[3H, CH3C(O)], 2.36 m (1Н, Н19), 3.75 d (1Н, Н28, J
2
11.1 Hz), 4.08 s (5НFc), 4.23 d (1Н, Н28, J 11.1 Hz),
4.33 s (2HFc), 4.46 m (1Н, Н3), 4.72 s (1Н, Н29), 4.76 m
(2Н, NCH2), 4.93 s (2HFc), 5.05 s (1H, H29), 7.41 s
(1H, H5'). 13С NMR spectrum, δ, ppm: 14.71, 16.00,
16.13, 16.45, 18.10, 20.89, 20.98, 21.28, 23.64, 26.96,
26.96, 27.90, 29.78, 31.27, 34.09, 34.28, 37.03, 37.40,
37.75, 38.37, 40.88, 42.67, 46.31, 49.85, 50.17, 55.32,
62.38, 66.52, 66.59, 68.61, 69.48, 75.30, 80.83,
112.04, 119.00, 149.25, 170.98. Found, %: C 69.05; H
8.02; N 5.37. C45H61FeN3O5. Calculated, %: C 69.31;
H 7.88; N 5.39.
30-Azidolup-20(29)-ene-3β,28-diyldibenzoate
(3c) was prepared in a similar way from 0.73 g
(1 mmol) of bromide 2с and 0.195 g (3 mmol) of
sodium azide in 35 mL of DMSO. Yield 0.373 g
(54%), colorless crystals, mp 129–131°С, [α]D29 +27.6
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 11 2019

FERROCENYLTRIAZOLES FROM 3β,28-DIACYLBETULIN: SYNTHESIS
1695
Engineer O.A. Maiorova for measuring the 1Н and 13С NMR
spectra, and Scientific Researcher A.V. Kharitonova for
performing elemental analysis.
30-(4-Ferrocenyl[1,2,3]triazol-1-yl)lup-20(29)-
en-3β,28-diyldipropionate (4b). Yield 298 mg (37%),
yellow foam, does not have a well-defined melting
point, plasticizes in the range 120–135°С, Rf 0.40. IR
spectrum, cm–1: 3004, 2943, 2873, 1732, 1462, 1391,
1356, 1276, 1217, 1189, 1106, 1083, 1047, 1017, 968,
878, 819, 756. 1Н NMR spectrum, δ, ppm: 0.83 s (3H,
Me), 0.84 s (3H, Me), 0.85 s (3H, Me), 0.99 s (3H, Me),
1.03 s (3H, Me), 1.13 t (3Н, СН3, 3J 7.2 Hz), 1.15 t (3Н,
СН3, 3J 7.2 Hz), 2.29 q [2Н, С(О)СН2, 3J 7.2 Hz], 2.31
FUNDING
The work was financially supported by the Russian
Foundation for Basic Research (project no. 16-33-00147)
and the “Basic Science for Medicine” Complex Program of
the Ural Branch of the Russian Academy of Sciences
(project no. 18-7-3-4).
3
q [2Н, С(О)СН2, J 7.2 Hz], 2.34 m (1Н, Н19), 3.76 d
(1Н, Н28, 2J 11.2 Hz), 4.05 s (5НFc), 4.26 d (1Н, Н28, 2J
11.2 Hz), 4.28 s (2НFc), 4.47 m (1Н, Н3), 4.70 s (1Н, Н29),
4.73 m (С30Н2), 4.92 s (2НFc), 5.05 s (1Н, Н29), 7.41 s
(1Н, Н5'). 13С NMR spectrum, δ, ppm: 9.15, 9.28, 14.75,
16.02, 16.11, 16.49, 18.13, 20.94, 22.77, 23.69, 26.93,
27.02, 27.63, 27.93, 28.03, 29.39, 29.86, 31.32, 34.14,
34.30, 37.08, 37.45, 37.87, 38.41, 40.94, 42.72, 43.87,
46.47, 49.95, 50.22, 54.64, 55.38, 62.13, 66.67, 68.65,
69.53, 75.47, 80.55, 112.05, 119.01, 147.02, 149.32,
174.20, 174.67. Found, %: C 70.34; H 8.17; N 4.94.
C47H65FeN3O5. Calculated, %: C 69.91; H 8.11; N 5.20.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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The authors express their gratitude to Engineer
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