Amides of N-Deacetyllappaconitine and Unsaturated Fatty Acids

Article abstract of DOI:10.1007/s10600-018-2518-5

Amides were prepared from N-deacetyllappaconitine and unsaturated oleic, linoleic, α-linolenic, and γ-linolenic fatty acids.

Full text of DOI:10.1007/s10600-018-2518-5

DOI 10.1007/s10600-018-2518-5
Chemistry of Natural Compounds, Vol. 54, No. 5, September, 2018
AMIDES OF N-DEACETYLLAPPACONITINE AND
UNSATURATED FATTY ACIDS
*
T. M. Gabbasov, E. M. Tsyrlina, and S. G. Yunusova
Amides were prepared from N-deacetyllappaconitine and unsaturated oleic, linoleic, α-linolenic, and
γ-linolenic fatty acids.
Keywords: diterpene alkaloids, N-deacetyllappaconitine, oleic acid, linoleic acid, α-linolenic acid, γ-linolenic acid.
Conjugates combining different pharmacophores represent a modern approach to new drug design. They are potentially
capable of expanding spectra of biological activity of known drugs, affecting the number of pathogenesis mechanisms, and
reducing the number of drugs used in complex therapy.
N-Deacetyllappaconitine (1), the main metabolite of allapinine, is just as active in most arrhythmia models as allapinine,
less toxic, and faster in onset of antiarrhythmic effects but has a shorter duration of action [1]. Modification of 1 is interesting
for producing new derivatives combining high arrhythmic activity, prolonged duration of action, and lower toxicity [2, 3].
Unsaturated fatty-acid chlorides could be used for modification and were previously added to the 8-position of aconitine-type
diterpene alkaloids [4].
OCH
16
3
1
3
1
2
H
3
CO
1
R =
1
7
OCH
OH
18''
3
9''
9''
14
0
1
O
2
3
15
N
8
3
OH
5
12''
19
6
O
O
O
1'
NHR
9''
12''
12''
15''
2'
O
4
9''
5'
6''
1
- 5
1
: R = H
O
5
Linoleic and α-linolenic essential polyunsaturated fatty acids (PUFAs) are known to be progenitors of two families of
higher PUFAs, i.e., ω-3 and ω-6, a deficiency of which could lead to a broad spectrum of illnesses. They are precursors of
prostaglandins and possess potent antisclerotic and cardioprotective activity. They reduce inflammation and cholesterol level
and decrease platelet aggregation. In general, this reduces the risk of cardiovascular diseases [5, 6].
Free fatty acids (FAs), primarily linoleic and palmitic [7], and lipoditerpene alkaloids with fatty-acid residues in
the 8-position [8] were observed in plants of the genus Aconitum among the natural constituents.
Unsaturated-acid chlorides [oleic (OA), linoleic (LA), α-linolenic (ALA), and γ-linolenic (GLA)] were chosen as
the modifiers for producing previously unreported amides. Commercial olive, sunflower, flaxseed, and Borago officinalis
seeds, lipids of which were characterized by significant contents of GLA [9, 10], were the main sources of the acids.
Neutral lipids were extracted by hexane from ground seeds. Fatty acids were isolated from the neutral lipids by
hydrolysis and as urea clathrates from the corresponding FAmixtures to produce fractions enriched in one acid or another [11].
The compositions of the FA fractions were monitored by GC of methyl esters. The total starting FAs used to produce
the concentrates were also analyzed (Table 1).
Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 71 Prosp. Oktyabrya, Ufa,
4
50054, Russian Federation, e-mail: tsirlina@anrb.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 5,
September–October, 2018, pp. 802–805. Original article submitted March 22, 2018.
0
009-3130/18/5405-0947 ©2018 Springer Science+Business Media, LLC
947

TABLE 1. Compositions of Fatty-Acid Concentrates of Neutral Lipids Before and After Separation of Clathrates, % of ΣFA
Oil
Seeds
Acid
olive
sunflower
flaxseed
B. officinalis
1
2
1
2
1
2
1
2
1
1
1
1
1
6:0
6:1
7:0
8:0
8:1
12.9
3.0
–
5.6
57.0
18.6
–
2.9
–
–
–
–
–
5.8
–
–
3.9
22.5
67.0
–
–
–
–
4.2
–
–
–
–
–
11.4
–
0.5
–
–
–
–
–
33.6
65.1
1.3
–
–
–
–
–
3.2
21.0
15.3
–
55.4
0.2
0.2
21.0
15.3
55.4
–
4.6
96.5
3.5
–
–
–
8.5
91.5
–
–
–
0.7
17.0
–
82.3
–
–
–
17.0
82.3
20.8
36.9
19.9
0.6
3.3
2.0
20.8
36.9
20.5
α-18:2
γ-18:3
α-18:3
2
2
Σmonoen
Σ
–
0:0
2:0
0.2
0.6
22.5
67.0
–
–
–
60.0
18.6
2.9
96.5
3.5
–
8.5
91.5
–
33.6
66.4
dien
Σtrien
_____
) Initial FA composition; 2) FA composition of concentrate.
_
1
Reaction of the OA, LA, ALA, and GLA concentrates with an excess of oxalyl chloride in anhydrous C H produced
6
6
the acid chlorides. The solvent and excess of oxalyl chloride were evaporated. The chlorides were used without further
separation in reactions with N-deacetyllappaconitine (1, CH Cl , Et N, 4 h).
2
2
3
Corresponding amides 2–4 were obtained in 58–63% yield; amide 5, in a mixture with 3 (2:1 ratio) in 59% yield.
1
3
The structures of the amides were established using PMR, C NMR, and DEPT and 2D COSY, HSQC, HMBC, and NOESY
correlation spectra and IR and mass spectra.
–
1
IR spectra of amides 2–5 showed NHCO stretching bands at 1681–1682 cm . The acyl groups in these compounds
1
3
were confirmed by additional resonances in PMR and C NMR spectra for CH at δ 0.87–0.88 ppm and δ 14.1–14.3 ppm
3
H
C
and proton and C-atom resonances of double bonds (δ 5.32–5.38 ppm; δ 127.1–131.9 ppm).
H
C
1
3
PMR and C NMR spectra of 2–5 had proton and C-atom chemical shifts for the basic C skeleton including
the aromatic ring and practically did not change except for the appearance of an Ar-NH-fragment at weak field of δ 11 ppm.
H
The appearance in this region that was analogous to that observed for ArNHAc of lappaconitine confirmed that the N atoms
were acylated to form the corresponding amides.
EXPERIMENTAL
GC analysis of methyl esters of FAs used a GC-2014 chromatograph (Shimadzu) with an Omegawax TM 250 capillary
column (30.0 m × 0.25 mm, Supelco), stationary phase poly(ethylene glycol) L (0.25 μm), column temperature 205°C, vaporizer
2
50°C, detector 260°C, and carrier gas He at flow rate 30 mL/min. IR spectra were recorded from films on a Shimadzu
–1
Prestige 21 FT-IR spectrophotometer in the range 4000–400 cm . Mass spectra were measured using direct sample introduction
into the ion source of a Thermo Finnigan MAT 95 XP mass spectrometer with programmed temperature from 50 to 270°C and
ionizing potential 70 eV. PMR and C NMR spectra were recorded in CDCl with TMS internal standard on a Bruker Avance
1
3
3
1
13
III-500 spectrometer [500.13 MHz ( H), 125.76 MHz ( C)].
13
Resonances in PMR and C NMR spectra were accurately assigned using NMR spectral recording methods embedded
1
3
in the spectrometer operating system, i.e., C-DEPT 135 and DEPT 90 with full proton decoupling, where the chemical shifts
CSs) of methyl, methylene, methine, and quaternary C atoms are determined unambiguously. Then, 2D HSQC CH-correlation
(
1
1
spectroscopy was used to find the CSs of protons bonded to the corresponding C atoms. The H– H COSY spectrum confirmed
the proton couplings. The HMBC spectrum indicated the correctness of the proton CS assignments from their couplings with
geminal and vicinal C atoms. Thus, proton CSs in the Experimental section were determined from 2D HSQC spectra.
GC analyses and spectral studies used equipment at the Khimiya CUC, UIC, RAS. Dried and freshly distilled solvents
were used in the work. Benzene was dried by distillation over CaH under Ar. Seed oil from B. officinalis was obtained by
2
948

extracting ground seeds in a Soxhlet apparatus. Commercially available olive, sunflower, and flaxseed oils were used to
isolate OA, LA, and ALA. FAs were isolated from oils by hydrolysis with KOH/MeOH (10%). Concentrates of OA, LA,
ALA, and GLA were produced by treating the corresponding acid mixture with saturated urea solution in EtOH (FA–urea, 1:3;
6
0°C, 1 h; room temp., 3 h; 10°C, 24 h). The concentrate of the corresponding acid was extracted from the mother liquor
(
H O, HCl, Et O) as before [11]. The quantitative content of acid in the mother liquor was estimated by methylating it with
2
2
CH N and analyzing it by GC.
2
2
General Method for Preparing FA Acid Chlorides. A solution of the appropriate FA (0.002 mol) in anhydrous
C H (15 mL) was stirred, treated with oxalyl chloride (0.19 mL, 0.0022 mol), held at room temperature under Ar for 6 h, and
6
6
evaporated in a rotary evaporator. The product was again dissolved in C H and evaporated to remove traces of oxalyl
6
6
chloride and dissolved in anhydrous CH Cl (15 mL) for subsequent acylation of N-deacetyllappaconitine (1).
2
2
General Method for Acylation of N-deacetyllappaconitine (1) by FA Chlorides. A solution of 1 (2 mmol) and
Et N (0.26 mL, 2 mmol) in anhydrous CH Cl (15 mL) was treated with a solution of the appropriate FA chloride.
3
2
2
The mixture was stirred at room temperature under Ar for 4 h. The course of the reaction was monitored by TLC. The mixture
was washed with soda solution (10%, 10 mL), dried over Na SO , and evaporated. The residue was dried in vacuo and
2
4
purified by column chromatography over SiO (60/150 μm) using C H –MeOH (0.5–2 vol%).
2
6 6
N-9-Octadecamonoenoyl-N-deacetyllappaconitine (2). Yield 58%. Mass spectrum (EI, 70 eV), m/z (I , %): 806
M , 1), 405 (100). IR spectrum (ÊÂr, ν, cm ): 1700 (Ñ=Î), 1681 (NHÑO), 1130–1080 (Ñ–Î). Í NMR spectrum
rel
+
–1
1
(
(
500 MHz, ÑDCl , δ, ppm, J/Hz): 0.88 (3Í, t, J = 7.0, Í-18′′), 1.13 (3Í, t, J = 7.1, ÑÍ ÑÍ N), 1.60 (1Í, dd, J = 15.0, 8.2,
3
3
2
Í -6), 1.81 (1Í, m, Í -3), 1.99 (1Í, m, Í -12), 2.04 (1Í, m, Í -15), 2.11 (1Í, m, Í-10), 2.17 (1Í, m, Í-7), 2.18 (1Í, m,
a
a
a
a
Í -2), 2.30 (1Í, m, Í -2), 2.38 (1Í, m, Í-13), 2.40 (1Í, m, Í -15), 2.42 (1Í, m, Í-5), 2.51 (1Í, m, Í -12), 2.52 (1Í, m,
a
b
b
b
ÑÍ ÑÍ N), 2.57 (1Í, d, J = 11.4, Í -19), 2.58 (1Í, m, ÑÍ ÑÍ N), 2.67 (1Í, m, Í -3), 2.71 (1Í, dd, J = 15.0, 7.5, Í -6), 3.02
3
à
a
3
b
b
b
(
1Í, s, Í-17), 3.19 (1Í, m, Í-1), 3.30 (3Í, s, 1-ÎÑÍ ), 3.31 (1Í, m, Í-16), 3.32 (3Í, s, 16-ÎÑÍ ), 3.41 (3Í, s, 14-ÎÑÍ ),
3 3 3
3
.45 (1Í, d, J = 4.6, Í-14), 3.60 (1Í, d, J = 11.4, Í -19), 5.34 (2Í, m, Í-9′′, 10′′), 7.02 (1Í, t, J = 7.6, Í-5′), 7.49 (1Í, t,
b
1
3
J = 7.4, 8.2, Í-4′), 7.92 (1Í, d, J = 8.1, Í-6′), 8.70 (1Í, d, J = 8.5, Í-3′), 11.07 (1Í, s, NÍ). C NMR spectrum (125 MHz,
ÑDCl , δ, ppm): 84.2 (ÑÍ, Ñ-1), 26.8 (ÑÍ , Ñ-2), 31.8 (ÑÍ , Ñ-3), 84.5 (Ñ, Ñ-4), 48.5 (ÑÍ, Ñ-5), 24.1 (ÑÍ , Ñ-6), 47.6 (ÑÍ,
3
2
2
2
Ñ-7), 75.6 (Ñ, Ñ-8), 78.6 (Ñ, Ñ-9), 49.8 (ÑÍ, Ñ-10), 51.0 (Ñ, Ñ-11), 26.2 (ÑÍ , Ñ-12), 36.3 (ÑÍ, Ñ-13), 90.1 (ÑÍ, Ñ-14), 44.8
2
(
ÑÍ , Ñ-15), 82.9 (ÑÍ, Ñ-16), 61.5 (ÑÍ, Ñ-17), 55.5 (ÑÍ , Ñ-19), 49.0 (ÑÍ , Ñ-21), 13.6 (ÑÍ , Ñ-22), 56.6 (ÑÍ , 1-OCH ),
2 2 2 3 3 3
5
7.9 (ÑÍ , 14-OCH ), 56.1 (ÑÍ , 16-OCH ), 167.5 (Ñ, 4-OCO), 115.8 (Ñ, Ñ-1′), 141.8 (Ñ, Ñ-2′), 120.3 (ÑÍ, Ñ-3′), 134.4
3 3 3 3
(
ÑÍ, Ñ-4′), 122.2 (ÑÍ, Ñ-5′), 131.1 (ÑÍ, Ñ-6′), 172.3 (Ñ, NÍCO), 38.7 (ÑÍ , Ñ-2′′), 25.5 (ÑÍ , Ñ-3′′), 29.2–29.8 (6 × ÑÍ ,
2 2 2
Ñ-4′′, 5′′, 6′′, 13′′, 14′′, 15′′), 29.8 (2 × ÑÍ , Ñ-7′′, 12′′), 27.1 (2 × ÑÍ , Ñ-8′′, 11′′), 129.8 (ÑÍ, Ñ-9′′), 130.0 (ÑÍ, Ñ-10′′), 31.9
2
2
(
ÑÍ , Ñ-16′′), 22.7 (ÑÍ , Ñ-17′′), 14.1 (ÑÍ , Ñ-18′′).
2
2
3
N-9,12-Octadecadienoyl-N-deacetyllappaconitine (3). Yield 63%. Mass spectrum (EI, 70 eV), m/z (I , %): 804
M , 1), 405 (100). IR spectrum (ÊÂr, ν, cm ): 1700 (Ñ=Î), 1682 (NHÑO), 1130–1180 (Ñ–Î). Í NMR spectrum (500 MHz,
rel
+
–1
1
(
ÑDCl , δ, ppm, J/Hz): 0.88 (3Í, t, J = 7.0, Í-18′′), 1.12 (3Í, t, J = 7.1, ÑÍ ÑÍ N), 1.59 (1Í, dd, J = 15.1, 8.3, Í -6), 1.80
3
3
2
a
(
1Í, m, Í -3), 1.98 (1Í, m, Í -12), 2.01 (1Í, m, Í -15), 2.10 (1Í, m, Í-10), 2.15 (1Í, m, Í-7), 2.17 (1Í, m, Í -2), 2.29 (1Í,
a a a a
m, Í -2), 2.37 (1Í, m, Í-13), 2.39 (1Í, m, Í-5), 2.40 (1Í, m, Í -15), 2.50 (1Í, m, Í -12), 2.51 (1Í, m, ÑÍ ÑÍ N), 2.54
b
b
b
3
a
(
1Í, d, J = 11.4, Í -19), 2.56 (1Í, m, ÑÍ ÑÍ N), 2.64 (1Í, m, Í -3), 2.68 (1Í, dd, J = 15.1, 7.4, Í -6), 3.00 (1Í, s, Í-17),
a 3 b b b
3
.18 (1Í, m, Í-1), 3.29 (3Í, s, 1-ÎÑÍ ), 3.30 (1Í, m, Í-16), 3.31 (3Í, s, 16-ÎÑÍ ), 3.40 (3Í, s, 14-ÎÑÍ ), 3.44 (1Í, d,
3 3 3
J = 4.7, Í-14), 3.58 (1Í, d, J = 11.4, Í -19), 5.35 (4Í, m, Í-9′′, 10′′, 12′′, 13′′), 7.01 (1Í, t, J = 7.6, Í-5′), 7.48 (1Í, t, J = 7.9,
b
1
3
Í-4′), 7.92 (1Í, d, J = 8.1, Í-6′), 8.70 (1Í, d, J = 7.9, Í-3′), 11.06 (1Í, s, NÍ). C NMR spectrum (125 MHz, ÑDCl , δ,
3
ppm): 84.2 (ÑÍ, Ñ-1), 26.8 (ÑÍ , Ñ-2), 31.8 (ÑÍ , Ñ-3), 84.5 (Ñ, Ñ-4), 48.6 (ÑÍ, Ñ-5), 24.1 (ÑÍ , Ñ-6), 47.6 (ÑÍ, Ñ-7), 75.6
2
2
2
(
Ñ, Ñ-8), 78.6 (Ñ, Ñ-9), 49.8 (ÑÍ, Ñ-10), 51.0 (Ñ, Ñ-11), 26.2 (ÑÍ , Ñ-12), 36.3 (ÑÍ, Ñ-13), 90.1 (ÑÍ, Ñ-14), 44.9 (ÑÍ ,
2
2
Ñ-15), 82.9 (ÑÍ, Ñ-16), 61.5 (ÑÍ, Ñ-17), 55.5 (ÑÍ , Ñ-19), 49.0 (ÑÍ , Ñ-21), 13.6 (ÑÍ , Ñ-22), 56.6 (ÑÍ , 1-OCH ), 57.9
2
2
3
3
3
(
ÑÍ , 14-OCH ), 56.1 (ÑÍ , 16-OCH ), 167.5 (Ñ, 4-OCO), 115.8 (Ñ, Ñ-1′), 141.8 (Ñ, Ñ-2′), 120.3 (ÑÍ, Ñ-3′), 134.4 (ÑÍ,
3 3 3 3
Ñ-4′), 122.2 (ÑÍ, Ñ-5′), 131.1 (ÑÍ, Ñ-6′), 172.2 (Ñ, NÍCO), 38.7 (ÑÍ , Ñ-2′′), 25.5 (ÑÍ , Ñ-3′′), 29.2–29.8 (5 × ÑÍ , Ñ-4′′,
2
2
2
5
′′, 6′′, 7′′, 15′′), 27.2 (2 × ÑÍ , Ñ-8′′, 14′′), 130.0 (ÑÍ, Ñ-9′′), 128.0 (ÑÍ, Ñ-10′′), 26.5 (ÑÍ , Ñ-11′′), 128.8 (ÑÍ, Ñ-12′′), 130.1
2
2
(
ÑÍ, Ñ-13′′), 31.5 (ÑÍ , Ñ-16′′), 22.6 (ÑÍ , Ñ-17′′), 14.1 (ÑÍ , Ñ-18′′).
2
2
3
N-9,12,15-Octadecatrienoyl-N-deacetyllappaconitine (4). Yield 61%. Mass spectrum (EI, 70 eV), m/z (I , %):
02 (M , 1), 405 (100). IR spectrum (ÊÂr, ν, cm ): 1700 (Ñ=Î), 1682 (NHÑO), 1130–1080 (Ñ–Î). Í NMR spectrum
rel
+
–1
1
8
(
500 MHz, ÑDCl , δ, ppm, J/Hz): 0.87 (3Í, t, J = 6.8, Í-18′′), 1.11 (3Í, t, J = 7.5, ÑÍ ÑÍ N), 1.59 (1Í, dd, J = 15.1, 8.3,
3
3
2
Í -6), 1.80 (1Í, m, Í -3), 2.00 (1Í, m, Í -12), 2.02 (1Í, m, Í -15), 2.09 (1Í, m, Í-10), 2.16 (1Í, m, Í-7), 2.18 (1Í, m,
a
a
a
a
949

Í -2), 2.29 (1Í, m, Í -2), 2.37 (1Í, m, Í-13), 2.39 (1Í, m, Í-5), 2.40 (1Í, m, Í -15), 2.49 (1Í, m, Í -12), 2.51 (1Í, m,
a
b
b
b
ÑÍ ÑÍ N), 2.54 (1Í, d, J = 11.4, Í -19), 2.56 (1Í, m, ÑÍ ÑÍ N), 2.65 (1Í, m, Í -3), 2.69 (1Í, dd, J = 15.1, 7.4, Í -6),
3
a
a
3
b
b
b
3
1
.00 (1Í, s, Í-17), 3.18 (1Í, m, Í-1), 3.29 (3Í, s, 1-ÎÑÍ ), 3.30 (1Í, m, Í-16), 3.31 (3Í, s, 16-ÎÑÍ ), 3.40 (3Í, s,
4-ÎÑÍ ), 3.44 (1Í, d, J = 4.6, Í-14), 3.58 (1Í, d, J = 11.4, Í -19), 5.32–5.38 (6Í, m, Í-9′′, 10′′, 12′′, 13′′, 15′′, 16′′), 7.01
3
3
3
b
(
1Í, t, J = 7.4, 7.8, Í-5′), 7.48 (1Í, t, J = 7.3, 7.9, Í-4′), 7.91 (1Í, d, J = 7.9, Í-6′), 8.69 (1Í, d, J = 8.5, Í-3′), 11.06 (1Í, s, NÍ).
1
3
C NMR spectrum (125 MHz, ÑDCl , δ, ppm): 84.2 (ÑÍ, Ñ-1), 26.8 (ÑÍ , Ñ-2), 31.8 (ÑÍ , Ñ-3), 84.5 (Ñ, Ñ-4), 48.6 (ÑÍ,
3
2
2
Ñ-5), 24.1 (ÑÍ , Ñ-6), 47.6 (ÑÍ, Ñ-7), 75.6 (Ñ, Ñ-8), 78.6 (Ñ, Ñ-9), 49.8 (ÑÍ, Ñ-10), 50.9 (Ñ, Ñ-11), 26.2 (ÑÍ , Ñ-12), 36.3
2
2
(
(
ÑÍ, Ñ-13), 90.1 (ÑÍ, Ñ-14), 44.8 (ÑÍ , Ñ-15), 82.9 (ÑÍ, Ñ-16), 61.6 (ÑÍ, Ñ-17), 55.5 (ÑÍ , Ñ-19), 49.0 (ÑÍ , Ñ-21), 13.6
ÑÍ , Ñ-22), 56.6 (ÑÍ , 1-OCH ), 57.9 (ÑÍ , 14-OCH ), 56.1 (ÑÍ , 16-OCH ), 167.4 (Ñ, 4-OCO), 115.8 (Ñ, Ñ-1′), 141.7 (Ñ,
2
2
2
3
3
3
3
3
3
3
Ñ-2′), 120.3 (ÑÍ, Ñ-3′), 134.4 (ÑÍ, Ñ-4′), 122.2 (ÑÍ, Ñ-5′), 131.1 (ÑÍ, Ñ-6′), 172.3 (Ñ, NÍCO), 38.7 (ÑÍ , Ñ-2′′), 25.5
2
(
ÑÍ , Ñ-3′′), 29.2–29.6 (4 × ÑÍ , Ñ-4′′, 5′′, 6′′, 7′′), 27.2 (ÑÍ , Ñ-8′′), 130.3 (ÑÍ, Ñ-9′′), 128.3 (ÑÍ, Ñ-10′′), 25.6 (ÑÍ ,
2 2 2 2
Ñ-11′′), 127.7 (ÑÍ, Ñ-12′′), 128.3 (ÑÍ, Ñ-13′′), 25.5 (ÑÍ , Ñ-14′′), 127.1 (ÑÍ, Ñ-15′′), 131.9 (ÑÍ, Ñ-16′′), 20.5 (ÑÍ , Ñ-17′′),
2
2
1
4.3 (ÑÍ , Ñ-18′′).
3
+
N-6,9,12-Octadecatrienoyl-N-deacetyllappaconitine (5). Mass spectrum (EI, 70 eV), m/z (I , %): 802 (M , 1),
rel
–
1
1
4
05 (100). IR spectrum (ÊÂr, ν, cm ): 1700 (Ñ=Î), 1682 (NHÑO), 1130–1080 (Ñ–Î). Í NMR spectrum (500 MHz, ÑDCl ,
3
δ, ppm, J/Hz): 0.87 (3Í, t, J = 6.7, Í-18′′), 1.11 (3Í, t, J = 7.1, ÑÍ ÑÍ N), 1.60 (1Í, dd, J = 15.1, 8.2, Í -6), 1.80 (1Í, m,
3
2
a
Í -3), 1.96 (1Í, m, Í -12), 2.02 (1Í, m, Í -15), 2.09 (1Í, m, Í-10), 2.15 (1Í, m, Í-7), 2.18 (1Í, m, Í -2), 2.29 (1Í, m,
a
a
a
a
Í -2), 2.37 (1Í, m, Í-13), 2.39 (1Í, m, Í-5), 2.40 (1Í, m, Í -15), 2.49 (1Í, m, Í -12), 2.51 (1Í, m, ÑÍ ÑÍ N), 2.54 (1Í,
b
b
b
3
a
d, J = 11.4, Í -19), 2.56 (1Í, m, ÑÍ ÑÍ N), 2.65 (1Í, m, Í -3), 2.69 (1Í, dd, J = 15.1, 7.4, Í -6), 3.00 (1Í, s, Í-17), 3.19
a
3
b
b
b
(
1Í, m, Í-1), 3.29 (3Í, s, 1-ÎÑÍ ), 3.30 (1Í, m, Í-16), 3.31 (3Í, s, 16-ÎÑÍ ), 3.40 (3Í, s, 14-ÎÑÍ ), 3.44 (1Í, d, J = 4.7,
3 3 3
Í-14), 3.59 (1Í, d, J = 11.4, Í -19), 5.32–5.38 (6Í, m, Í-6′′, 7′′, 9′′, 10′′, 12′′, 13′′), 7.01 (1Í, t, J = 7.4, Í-5′), 7.48 (1Í, t,
b
1
3
J = 7.5, 8.0, Í-4′); 7.91 (1Í, d, J = 7.7, Í-6′), 8.69 (1Í, d, J = 8.5, Í-3′), 11.07 (1Í, s, NÍ). C NMR spectrum (125 MHz,
ÑDCl , δ, ppm): 84.2 (ÑÍ, Ñ-1), 26.8 (ÑÍ , Ñ-2), 31.8 (ÑÍ , Ñ-3), 84.5 (Ñ, Ñ-4), 48.5 (ÑÍ, Ñ-5), 24.1 (ÑÍ , Ñ-6), 47.6 (ÑÍ,
3
2
2
2
Ñ-7), 75.7 (Ñ, Ñ-8), 78.6 (Ñ, Ñ-9), 49.8 (ÑÍ, Ñ-10), 51.0 (Ñ, Ñ-11), 26.2 (ÑÍ , Ñ-12), 36.3 (ÑÍ, Ñ-13), 90.1 (ÑÍ, Ñ-14), 44.8
2
(
ÑÍ , Ñ-15), 82.9 (ÑÍ, Ñ-16), 61.6 (ÑÍ, Ñ-17), 55.5 (ÑÍ , Ñ-19), 49.0 (ÑÍ , Ñ-21), 13.5 (ÑÍ , Ñ-22), 56.6 (ÑÍ , 1-OCH ),
2 2 2 3 3 3
5
7.9 (ÑÍ , 14-OCH ), 56.1 (ÑÍ , 16-OCH ), 167.5 (Ñ, 4-OCO), 115.8 (Ñ, Ñ-1′), 141.7 (Ñ, Ñ-2′), 120.3 (ÑÍ, Ñ-3′), 134.4
3 3 3 3
(
ÑÍ, Ñ-4′), 122.3 (ÑÍ, Ñ-5′), 131.1 (ÑÍ, Ñ-6′), 172.1 (Ñ, NÍCO), 38.5 (ÑÍ , Ñ-2′′), 25.1 (ÑÍ , Ñ-3′′), 29.2 (ÑÍ , Ñ-4′′),
2 2 2
2
7.2 (ÑÍ , Ñ-5′′), 130.4 (ÑÍ, Ñ-6′′), 128.4 (ÑÍ, Ñ-7′′), 25.6 (ÑÍ , Ñ-8′′), 128.1 (ÑÍ, Ñ-9′′), 128.1 (ÑÍ, Ñ-10′′), 25.6 (ÑÍ ,
2 2 2
Ñ-11′′), 127.6 (ÑÍ, Ñ-12′′), 129.7 (ÑÍ, Ñ-13′′), 27.2 (ÑÍ , Ñ-14′′), 29.6 (ÑÍ , Ñ-15′′), 31.5 (ÑÍ , Ñ-16′′), 22.6 (ÑÍ ,
2
2
2
2
Ñ-17′′), 14.1 (ÑÍ , Ñ-18′′).
3
ACKNOWLEDGMENT
The work was performed under state task topic No. AAAA-A-17-117011910025-6.
REFERENCES
1
2.
.
M. S. Yunusov, Izv. Akad. Nauk, Ser. Khim., 620 (2011).
S. A. Ross and S. W. Pelletier, Heterocycles, 32 (7), 1307 (1991).
3
4.
.
V. E. Romanov, E. E. Shul′ts, M. M. Shakirov, and G. A. Tolstikov, Chem. Nat. Compd., 44, 346 (2008).
Y. Bai, H. K. Desai, and S. W. Pelletier, J. Nat. Prod., 57 (7), 963 (1994).
5
6.
.
J. L. Guil Guerrero, Eur. J. Lipid Sci. Technol., 109, 1226 (2007).
A. Y. Leung and S. Foster, Encyclopedia of Common Natural Ingredients, Used in Foods, Drugs and Cosmetics,
2
nd Ed., John Wiley & Sons Inc., New York, 1995.
7
.
E. Nyirimigabo, Y. Xu, Y. Li, Y. Wang, K. Agyemang, and Y. Zhang, J. Pharm. Pharmacol., 67 (1), 1 (2015).
D. Csupor, P. Forgo, E. M. Wenzig, R. Bauer, and J. Hohmann, J. Nat. Prod., 71, 1779 (2008).
S. S. Layshenko, S. G. Yunusova, M. S. Yunusov, E. G. Galkin, and O. N. Denisenko, Bashk. Khim. Zh.,
No. 4, 24 (2010).
8
.
9.
10.
S. G. Yunusova, L. I. Khatmulina, N. I. Fedorov, N. A. Ermolaeva, E. G. Galkin, and M. S. Yunusov,
Chem. Nat. Compd., 48, 361 (2012).
11.
S. G. Yunusova, Chem. Nat. Compd., 49, 85 (2013).
950