N-allylisonitrarine and narcissin from plants of the Nitraria genus

Article abstract of DOI:10.1023/A:1014431712611

The new alkaloid N-allylisonitrarine was isolated from the aerial part of Nitraria schoberi L. Its structure was established using spectral data and chemical transformations. Leaves of Nitraria komarovii contain the flavonoid narcissin. Its ¹H

Full text of DOI:10.1023/A:1014431712611

Chemistry of Natural Compounds, Vol. 37, No. 5, 2001
N-ALLYLISONITRARINE AND NARCISSIN FROM
PLANTS OF THE
GENUS
Nitraria
T. S. Tulyaganov,1 O. M. Nazarov,2
O. E. Makhmudov,2 A. D. Vdovin,1
and N. D. Abdullaev1
UDC 547.944/945+547.942
Nitraria schoberi
Nitraria komarovii
The new alkaloid N-allylisonitrarine was isolated from the aerial part of
was established using spectral data and chemical transformations. Leaves of
flavonoid narcissin. Its 1H and 13C NMR spectra were studied.
L. Its structure
contain the
Key words:
,
,
, alkaloid N-allylisonitrarine, flavonoid narcissin.
Nitraria Nitraria schoberi Nitraria komarovii
In continuation of the investigation of the aerial part of
L. [1], an optically inactive base 1 with mp
Nitraria schoberi
257-258oC (ethanol), molecular weight 347 (mass spectrum), and formula C22H29N3 was isolated by column chromatography
from the CHCl fraction of the total bases.
3
The UV spectrum of 1 contains the following absorption maxima (
, C H OH): 223, 266-271, 280 (sh), 389 nm
λmax
2 5
(log 4.74, 3.83, 3.80, and 3.48). These are characteristic of a nonconjugated indole chromophore [2].
ε
The IR spectrum of 1 contains absorption bands characteristic of an -disubstituted benzene ring (743 cm-1), a
o
substituted indole (1451, 1473, 1572, and 1523 cm-1), and an isolated double bond (1640 cm-1), etc.
The PMR spectrum exhibits signals typical of an allyl (3.31 ppm, d, 2H, J = 9.5 Hz; 5.24, m, 2H; 5.86, m, 1H) and
aromatic and alicyclic protons.
The spectral data indicate that 1 is an indole derivative. The alkaloid N-allylnitrarine with the identical formula and
molecular weight was isolated from this genus but differs in melting point [3]. Therefore, we supposed that 1 is an isomer of
this alkaloid. Apparently, 1 isolated by us is N-allylisonitrarine, an epimer of nitrarine at C-3. The N-allyl derivative of
isonitrarine synthesized by us is identical to 1.
Thus, 1 is a new alkaloid and has the structure N-allylisonitrarine.
N
N
N
N
H
N
H
H
H
H
H
CH CH CH Br
2
2
H
H
HN
1
2
We investigated the components of leaves of
Iljin et Lava [3, 4] collected in June 1987 near
Nitraria komarovii
Turkmenbashi (Krasnovodsk, Republic of Turkmenistan) during flowering.
Alkaloids were extracted from by a modified method (described in Experimental).
N. komarovii
Chromatography of the ethylacetate fraction over a silica-gel column with CHCl —CH OH gradient elution
3
3
afforded 3.
1) S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan,
Tashkent, fax (99871) 120 64 75, e-mail: cnc@icps.org.uz; 2) Fergana State University. Translated from Khimiya Prirodnykh
Soedinenii, No. 5, pp. 400-402, September-October, 2001. Original article submitted November 5, 2001.
0009-3130/01/3705-0470$25.00 ©2001 Plenum Publishing Corporation
470

TABLE 1. 13C NMR Chemical Shifts of Narcissin (3) and Isorhamnetin (4)
Narcissin
C atom
Isorhamnetin
Flavone
D-Glucose
L-Rhamnose
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-1
C-2
C-3
C-4
C-5
C-6
O-CH3
156.6s
133.2s
177.5s
156.6s
98.9d
147.4s
135.7s
175.9s
156.2s
98.4d
164.2s
94.2s
164.2s
93.6d
161.8s
104.2s
121.2s
113.5d
147.1s
149.6s
115.4d
122.5d
55.8q
160.6s
103.1s
120.3s
111.9d
147.4s
149.0s
115.6d
121.7d
55.8q
101.3*d
74.4d
100.9*d
4.4d
76.5d
70.7**d
71.9d
70.4d**
76.5d
68.4d
66.9t
17.8q
______
*, **Signals marked with the same symbol may be reversed.
Compound 3. Yellow crystals, C28H32O16, mp 201-203 C. The UV spectrum contains the following absorption
maxima (λmax, C H OH): 208, 256, 270, 362 nm (log ε 4.56, 3.97, 3.85, 3.74) that change upon basicification (λmax, C H OH
2
5
2 5
-
+ OH ): 210, 276, 422 nm [5, 6].
The PMR spectrum recorded in a CD OD—CDCl (3:1) mixture exhibits signals (δ, ppm, J/Hz): 1.07 (3H, d, J = 6,
3
3
CH of rhamnose); 3.2-3.7 and 4.55-5.00 (carbohydrate); 4.48 (1H, s, anomeric proton of α-L-rhamnose), 5.05 (1H, d, J = 7.5,
3
anomeric proton of β-D-glucose), 3.90 (3H, s, Ar-OMe), 6.19 (1H, d, J = 2.5, H-6), 6.35 (1H, d, J = 2.5, H-8), 6.88 (1H, d,
J = 9.5, H-5 ), 7.61 (1H, dd, J = 9.5, J = 1.5, H-6 ), and 7.90 (1H, d, J = 1.5, H-2 ).
o
+
Acid hydrolysis of 3 afforded isorhamnetin [6, 7], C16H12O7, mp 306-308 C, [M] 316. UV spectrum ( max, C H OH):
2
5
208, 257, 270, 372 nm.
PMR spectrum (C D N, δ, ppm, J/Hz): 3.87 (3H, s, Ar-OMe), 6.09 (1H, d, J = 2.5, H-6), 6.44 (1H, d, J = 2.6, H-8),
5
5
6.85 (1H, d, J = 8.5, H-5 ), 7.55 (1H, d, J = 2.5, H-2 ), 7.62 (1H, dd, J = 8.5, J = 2.5, H-6'). We also identified D-glucose and
L-rhamnose.
Acetylation of 3 by acetic anhydride in pyridine produced the nonaacetyl derivative of formula C46H50O25 with mp 120-
122oC. The mass spectrum contains a peak for the molecular ion (1002) and strong peaks for fragment ions acetylated biose
with m/z 561 and terminal rhamnose with m/z 273, 213, and 153 [8].
Partial hydrolysis of 3 by acetic acid (10%) produced the 3-O-β-D-glucopyranoside of isorhamnetin (5), C22H22O12,
mp 171-173oC. UV spectrum (λmax, C H OH): 208, 256, 271, 365 nm [9].
2
5
The location of the carbohydrates in the studied flavonoid was determined by comparing the 13C NMR spectra of 3 and
its hydrolysis product, isorhamnetin (4). Signals were assigned based on literature data [10, 11], the results of which are listed
in Table 1.
Signals for C-2, C-3, and C-4 appear in the 13C NMR spectrum of 3 at 156.6, 133.2, and 177.5 ppm, respectively; in
that of its hydrolysis product, at 147.4, 135.7, and 175.9 ppm. The chemical shifts of these C atoms that are induced by
glycosylation (ICS) are +9.2, +2.5, and -1.6 ppm, respectively. These same values have been reported [10, 11]. The anomalous
shift induced for C-2 is explained by the partially olefinic nature of the C-2–C-3 bond.
This anomaly is evidently caused by keto—enol tautomerism in flavon-3-ols:
471

OCH
OCH
3
3
OH
OH
HO
O
O
HO
O
O
H
O
OH
OH
OH
7
6
If the inversion occurs rapidly, the 13C NMR spectrum exhibits signals that are averaged over the two tautomers (6 and
7), i.e., signals of the equilibrium state of 4 appear. Such a situation is impossible for 3. This probably explains the rather large
3
ICS for C-2 because of the lack of a contribution from tautomer 7 with an sp -hybridized C-2.
Molecular mechanics (MM2) and semi-empirical PM3 calculations showed that the energy of enol 6 is 84.92 kcal/mol;
of the keto tautomer 7, 85.46 kcal/mol, i.e., the difference between them is only 0.44 kcal/mol. At room temperature, one form
can freely transform into the other. As a result, the NMR spectrum reflects the equilibrium state of the two rapidly
interconverting forms 6 and 7.
Thus, 3 is narcissin (isorhamnetin-3-O-rutinoside) [5]. It is isolated for the first time from this genus.
The alkaloids komavine and acetylkomavine [4], schoberine, nitramarine, dehydroschoberine, nitraraine,
tetramethylenetetrahydro- -carboline, nitraramine, desoxyvasicinone, nitraroxine, nitraramine N-oxide, and komarovine [12a-j,
β
respectively] were isolated by column chromatography by a modified method from the ether fraction of the total alkaloids of
N.
.
komarovii
The CHCl fraction of the total bases gave by column chromatography nitrarine, isonitrarine, nitramidine, schoberidine,
3
and nitraramine.
EXPERIMENTAL
UV spectra were recorded in alcohol on a Perkin—Elmer Lambda 16 spectrometer; mass spectra, in an MX-1310
spectrometer and a Kratos MS 25RF GC-MS; IR spectra, on a Perkin—Elmer System 2000 FT-IR in KBr pellets; 1H and 13
C
NMR spectra, in a CDCl —CD OD mixture on a Tesla BS 567A spectrometer. Chemical shifts were measured relative to
3
3
HMDS (1H) and TMS (13C) standards.
The purity of the compounds was checked by TLC using silica gel (KSK and L 5/40) and Silufol UV-254 plates.
The following solvent systems were used for chromatography: CHCl —CH OH (8:1), CHCl —C H OH (8:1),
3
3
3
2 5
CHCl —OC(CH ) —CH OH
(5:4:1),
CHCl —CH OH
(4:1),
CHCl —C H OH—NH OH
(8:2:0.1),
3
3 2
3
3
3
3
2
5
4
CHCl —CH OH—NH OH(8:2:0.1), CHCl —OC(CH ) —C H OH—NH OH(5:4:1:0.1), -butanol—pyridine—water (6:4:3).
n
3
3
4
3
3 2
2
5
4
Dragendorff's solution and iodine and ammonia vapor were used as developers.
Sugar was detected by paper chromatography (PC) using FN-13 paper (Germany) with spraying by acid anilinium
phthalate and subsequent heating for 3-5 min at 90-100oC.
The extraction and isolation of the total bases from
L. has been described in detail [1].
N. schoberi
N-Allylisonitrarine. Chromatographic fractions 18-24 were combined and crystallized from ethanol to give 1, 63 mg,
mp 257-258oC.
+
Mass spectrum, / ( , %): 347 [M] (45), 320 (10), 319 (11), 318 (12), 306 (59), 289 (10), 277 (12), 263 (28), 243
m z Irel
(38), 237 (43), 225 (98), 224 (100), 222 (83), 221 (94), 169 (54), 168 (62), 144 (72).
IR spectrum (KBr,
, cm-1): 743, 773, 852, 892, 924, 937, 951, 1009, 1122, 1143, 1232, 1334, 1445, 1468, 1640,
νmax
2744, 2814, 2863, 2937, 3046.
PMR spectrum (CD OD + CDCl , , ppm, J/Hz): 1.62 (m), 2.08 (m), 2.75 (m), 3.12 (m), 3.31 (2H, d, J = 9.5), 4.38
δ
3
3
(m), 4.68 (1H, br.s), 5.24 (2H, m), 5.86 (2H, m), 7.11 (2H, m), 7.42 (2H, m).
Alkylation of Isonitrarine by Allylbromide. N-Allylisonitrarine. A solution of isonitrarine (2, 0.2 g) in ethanol
(5 mL) was treated with freshly distilled allylbromide (2 mL) and refluxed for 5 h. After the reaction was finished the solvent
was removed, water was added, and the solution was basicified with KOH (10%) and extracted with CHCl . The CHCl was
3
3
removed. The solid was separated by chromatography over a silica-gel column with elution by CHCl —C H OH (5:1) to give
3
2 5
472

N-allylisonitrarine, 0.13 g, mp 257-258oC (ethanol).
Extraction of N. komarovii Leaves. Finely ground leaves (2.3 kg) were extracted with ethanol (10 times). All extracts
were combined and condensed. The concentrated solution was washed with hexane (5 times) and diluted with an equal volume
of H SO (5%). The aqueous alcoholic solution was washed with ethylacetate and n-butanol to give ethylacetate (9.3 g) and
2
4
n-butanol (16.8 g) fractions of total compounds. The overall yield was 26.1 g or 1.13% of the air-dried mass.
The acidic solution was basicified with NaOH (10%). Bases were extracted by ether and then CHCl , adding NH Cl.
3
4
The phenolic fraction was extracted by CHCl . The following alkaloid fractions were obtained: nonphenolic part, ether
3
2.17 g, CHCl 9.61 g; phenolic part, CHCl 0.32 g. Overall yield 12.10 g or 0.53% of the air-dried mass.
3
3
Narcissin. The ethylacetate fraction (9.3 g) was chromatographed over a silica-gel column with elution by
CHCl —CH OH mixtures (50:1, 20:1, 10:1, 5:1, and 4:1). Fractions of 120-150 mL were collected. Fractions 37-45 were
3
3
evaporated and crystallized from CH OH to give 3, 0.31 g, mp 201-203oC.
3
IR spectrum (KBr, νmax, cm-1): 854, 712, 806, 832, 922, 1033, 1061 (glycoside C–O), 1125, 1167, 1181, 1206, 1359,
1431, 1455, 1504, 1557, 1603 (aromatic C C), 1656 (γ -pyrone C O), 2920 (O–CH ), 3277 (OH).
3
PMR spectrum (DMSO-d , δ, ppm, J/Hz): 0.95 (3H, d, J = 5.5), 2.88-3.75 (D-glucose and L-rhamnose), 3.83 (3H, s,
6
Ar-OMe), 4.41 (1H, s, L-rhamnose anomeric H), 5.38 (1H, d, J = 7.5, D-glucose anomeric H), 6.92 (1H, d, J = 1.5, H-6), 6.43
(1H, d, J = 1.5, H-8), 6.90 (1H, d, J = 9, H-5 ), 7.53 (1H, dd, J = 9, J = 1.5, H-6 ), 7.84 (1H, d, J = 1.5, H-2 ). Properties of the
PMR spectrum of 3 in CD OD + CDCl are given in the text.
3
3
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