Oxidation of aconitine by potassium permanganate. A new N-de-ethyl-7,17-secoimino derivative

Article abstract of DOI:10.1007/s10600-010-9492-x

The alkaloid aconitine was oxidized by potassium permanganate in aqueous acetone. It was shown that the oxidation formed three products including the previously described N-de-ethylaconitine, N-de-ethyl-19-oxoaconitine, and a new N-de-ethyl-7,17-secoimino

Full text of DOI:10.1007/s10600-010-9492-x

Chemistry of Natural Compounds, Vol. 45, No. 6, 2009
OXIDATION OFACONITINE BY POTASSIUM PERMANGANATE.
A NEW N-DE-ETHYL-7,17-SECOIMINO DERIVATIVE
M. N. Sultankhodzhaev
UDC 547.944/945
The alkaloid aconitine was oxidized by potassium permanganate in aqueous acetone. It was shown that the
oxidation formed three products including the previously described N-de-ethylaconitine, N-de-ethyl-19-
oxoaconitine, and a new N-de-ethyl-7,17-secoimino derivative. The structure of the new product was proposed
13
based on spectral data (IR, mass, PMR and C NMR spectra).
Key words: diterpenoid alkaloid, aconitine, KMnO oxidation, new N-de-ethyl-7,17-secoimino derivative.
4
Oxidation of diterpenoid alkaloids by KMnO is one method for removing an alkyl substituent from the N atom [1].
4
The course of the reaction depends on the stereochemistry of the C-6 methoxy group, which sterically shields the more
reactive C-19 ring methylene in the case of its α-orientation, as occurs in aconitine (1), so that the permanganate ion attacks
primarily the N-ethyl group. It has been reported that oxidation of 1 by KMnO in acetone:water (50%) for 20 min produced
4
N-de-ethyl-19-aconitine (2, 30%), N-de-ethyloxoaconitine (3, 31%), and starting material (1, 27%) [1].
In order to prepare 2, we oxidized aconitine under analogous conditions and produced the desired product (28%),
N-de-ethyl-19-oxoaconitine (3, 32%), and a new crystalline N-de-ethyl-7,17-secoimino derivative (4, 30%). The product had
–1
formula C H NO (HRMS). The IR spectrum contained absorption bands for hydroxyls (3376 cm ), ester carbonyl (1728),
30 39
9
13
and ether (1107). Table 1 lists the PMR and C NMR data. Resonances were assigned by comparison with spectra of
secojesaconitine [2] and other related alkaloids [3, 4]. According to the PMR spectrum, the product contained four methoxyls
and C-14 benzoyl aromatic protons. However, resonances for N-ethyl and acetoxy were missing from the spectrum. The PMR
spectrum of 4 showed resonances for two olefinic protons. The resonance of the C-7 olefinic proton was observed at 5.62 ppm
as a broad doublet of doublets (J = 2.7 Hz, J = 3.9 Hz) and the C-17 proton at 7.83 ppm as a doublet (J = 1.7 Hz). Resonances
of olefinic C atoms at 137.8 (C-7), 137.7 (C-8), and 165.1 (C-17) in the C NMR spectrum confirmed that there were C-7–
C-8 and N–C-17 double bonds. The lack of acetoxyl and N-ethyl groups in the oxidation product indicated that the C-7–C-17
bond had cleaved with loss of acetyl and N-ethyl groups and formation of C-7–C-8 and N–C-17 double bonds.
1
2
13
OH
OH
OH
OCH
OH
OCH
OH
3
3
OCH
OH
3
H CO
3
H CO
3
H CO
3
OBz
OAc
OBz
OBz
N
N
H
N
R
OAc
HO
O
HO
CH O
HO
CH O
OCH
OCH
3
OCH
3
3
3
3
CH O
3
4
3
1, 2
1: R = C H ; 2: R = H
2
5
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: niruno@mail.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 708–
709, November–December, 2009. Original article submitted April 20, 2009.
©
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0009-3130/09/4506-0844 2009 Springer Science+Business Media, Inc.

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TABLE 1. PMR (400 MHz, CDCl , ppm) and C NMR (100.6 MHz, CDCl , ppm) Spectra of N-De-ethyl-7,17-secoimino
3
3
Derivative 4
C atom
C atom
16
17
18
δÑ
δH
δÑ
δH
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
79.5
33.0
71.0
47.9
43.6
87.0
137.8
137.7
42.7
41.5
51.5
38.6
73.9
79.5
79.2
1.10 (dd, J = 10.0, 5.00)
3.82 (dd, J = 10.0, 5.00)
79.2
92.1
76.5
51.5
56.8
57.9
61.6
59.0
166.3
133.2
131.0
129.9
128.5
129.9
131.0
3.33 (d, J = 5.2)
7.83 (d, J = 1.7)
3.71, 3.74 (d, J = 9.01)
2.13, 3.29 (d, J = 11.2)
19
1-OCH3
6-OCH3
16-OCH3
18-OCH3
Ar-CO
Ar-C-1′
3.20
3.22
3.76
3.31
4.48 (dtd, J = 2.2, 2.3, 2.2)
5.62 (br.dd, J = 2.7, 3.9)
8.03 (d, J = 8.1)
7.43 (t, J = 7.7)
7.56 (t, J = 7.4)
7.43 (t, J = 7.7)
8.03 (d, J = 8.1)
Ar-C-2
′
Ar-C-3
′
Ar-C-4
′
5.09 (d, J = 4.2)
4.82 (dd, J = 2.6, 2.7)
Ar-C-5′
Ar-C-6
′
EXPERIMENTAL
IR spectra in KBr disks were recorded on a Vector 22 spectrometer; mass spectra, in a JMS 600 H instrument using
13
electron impact. PMR and C NMR spectra in CDCl were taken from a Bruker instrument at operating frequencies 400 and
3
100.6 MHz, respectively, with TMS internal standard. TLC used KSK silica gel and solvent systems CHCl :CH OH (10:1,
3
3
50:1, 100:1) and C H :CH OH (4:1).
6
6
3
Oxidation of Aconitine (1) by KMnO . A solution of aconitine (1 g) in purified acetone (100 mL) was treated at
4
room temperature with KMnO (1 g) dissolved in acetone:water (200 mL, 50%) and shaken for 20 min. The excess of KMnO
4
4
was decomposed by sodium sulfite. The resulting precipitate of MnO was filtered off. Acetone was distilled from the mother
2
liquor. The cooled aqueous solution was acidified with H SO (2%) until the solution was acidic. The acidic solution was
2
4
washed with benzene (4×). Solvent was distilled to afford crystalline N-de-ethyl-19-oxoaconitine (3, 0.32 g), mp 265–267°C
(acetone). Then the acidic solution was made basic with Na CO and extracted with CHCl . The extract was dried over
2
3
3
Na SO . Solvent was removed. The solid was chromatographed over a column of deactivated Al O with elution by benzene
2
4
2 3
with gradual addition of MeOH. The benzene and benzene:MeOH (50:1) effluents afforded with the use of acetone crystalline
N-de-ethyl 7,17-secoimino derivative 4 (0.3 g). Elution by benzene:MeOH (25:1, 10:1, 1:1) afforded amorphous 2 (0.28 g).
N-De-ethyl-7,17-secoaconitine (4). C H NO (HRMS 557.26859, calcd 557.27503), mp 232–234°C (acetone).
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9
–1
IR spectrum (ν , cm ): 3376, 2932, 2885, 2832, 1728, 1637, 1600, 1493, 1465, 1451, 1415, 1379, 1352, 1318,
max
1285, 1264, 1225, 1198, 1183, 1107, 1080, 1076, 1048, 987, 964, 933, 915, 873, 715, 669, 642, 612, 595.
+
Mass spectrum (m/z, %): 557 (1.8) [M] , 542 (3.1), 526 (20.3), 104 (100), 59 (5.0).
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Table 1 lists the PMR and C NMR spectra.
ACKNOWLEDGMENT
The work was supported financially by the Academy of Sciences of the Republic of Uzbekistan (Grant FA-F3-T.147).
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