A new amide from Zanthoxylum armatum

Article abstract of DOI:10.1021/np980224j

A new amide designated as armatamide (1) - along with two lignans, asarinin and fargesin, α- and β-amyrins, lupeol, and β-sitosterol-β-D- glucoside - has been isolated from the bark of Zanthoxylum armatum. The structure of the new compound was deduced by spectral and chemical analysis as N-(4'-methoxyphenyl ethyl)-3, 4-methylenedioxy cinnamoyl amide.

Full text of DOI:10.1021/np980224j

J . Nat. Prod. 1999, 62, 311-312
311
A New Am id e fr om Za n th oxylu m a r m a tu m †
Narendra K. Kalia,‡ Bikram Singh,* and Ram P. Sood
Natural Plant Products Division, Institute of Himalayan Bioresource Technology,
Palampur - 176 061 Himachal Pradesh, India
Received May 29, 1998
A new amide designated as armatamide (1)salong with two lignans, asarinin and fargesin, R- and
â-amyrins, lupeol, and â-sitosterol-â-D-glucosideshas been isolated from the bark of Zanthoxylum
armatum. The structure of the new compound was deduced by spectral and chemical analysis as N-(4′-
methoxyphenyl ethyl)-3, 4-methylenedioxy cinnamoyl amide.
Zanthoxylum armatum DC [syn. Z. alatum Roxb.] (Ru-
taceae) is extensively used in the Indian system of medi-
cines as a carminative, stomachic, and anthelmintic. The
bark is pungent, and sticks prepared from it are used for
preventing toothache. The fruits and seeds are employed
as an aromatic tonic in fever, dyspepsia, and expelling
roundworms.1 Previous phytochemical examinations of Z.
armatum have afforded four lignans and an alkaloid,2 in
addition to other secondary metabolites.3 Here, we describe
the isolation and characterization of a new amide, armata-
mide (1), along with six previously reported compounds.
The known compounds were identified as R- and â-amyrins,
lupeol, and â-sitosterol â-D-glucoside from the hexane
extract and two lignans, asarinin and fargesin, from the
chloroform extract. The identities of the known compounds
were confirmed with the help of published spectral data
and mixture melting points.4,5
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Melting points were
determined with a Mettler digital instrument FP80 and are
uncorrected. The UV spectra were recorded on a Hitachi model
150-20. The IR spectra were taken on a Perkin-Elmer 399
instrument (KBr pellets). NMR spectra were recorded on a
Bruker AC-200 P instrument at 200 MHz for 1H and 50 MHz
for 13C, using TMS as internal standard. The MS were obtained
on a J EOL J MS-D300 mass spectrophotometer with a J MA-
2000 data processing unit.
TLC was performed on Si gel-G and were visualized with
iodine vapors and/or alcoholic H2SO4 acid followed by heating
at 110 °C. Si gel (60-120 mesh) was used for column chroma-
tography.
P la n t Ma ter ia l. The bark of Z. armatum was collected from
Palampur in Himachal Pradesh (alt. 1400 m) in 1992. The
plant material was identified, and a voucher specimen (no.
10989) was deposited in the Herbarium of the Regional
Research Laboratory, Canal Road, J ammu Tawi -180 001,
India.
Extr a ction a n d Isola tion . Dried, powdered bark (4 kg) of
plant was exhaustively extracted with MeOH for 72 h at room
temperature. The solvent was evaporated under vaccum to give
220 g of MeOH extract, 60 g of which was redissolved in
MeOH-H2O (1:1) and partitioned with n-hexane and then
CHCl3. The solvents were removed in vacuo. The hexane
extract (6.0 g) on repeated column chromatographic separation
led to the isolation of R- and â-amyrin, lupeol, and â-sitosterol-
â-D-glucoside. From the CHCl3 extract, asarinin, fargesin
(lignans), and armatamide (1) were isolated.
Armatamide (1), a white crystalline compound, was
determined to have a molecular formula of C19H19NO4 on
the basis of its molecular ion peak at m/z 325 (M+) in the
EIMS. UV absorption peaks were observed for a highly
unsaturated system that, on alkali addition, remained
unaltered, thus confirming the absence of phenolic func-
tions.6,7 In the 1HNMR spectrum, characteristic signals for
a methylenedioxy as a sharp singlet at δ 6.00, and a trans
pair of doublets at δ 6.16 (J ) 15.5 Hz) and 7.50 (J ) 15.5
Hz) and an aromatic methoxy group (δ 3.80, singlet) were
observed. A triplet at δ 2.78, (J ) 6.9 Hz) and a quartet at
δ 3.58 (J ) 6.9 Hz) were assigned for two methylenes
attached to an amide moiety.8 The 13C NMR also cor-
roborated the proposed structure. Diagnostic signals were
readily observed and assigned as δC 163.60 (CdO), 55.45
(-OCH3), 101.36 (O-CH2-O), 140.91, 129.79 (HCdCH)
35.07, 41.09 (CH2CH2NH). The structure assigned as N-(4′-
methoxyphenyl ethyl)-3,4-methylenedioxy cinnamoyl amide
was confirmed by an unambiguous synthesis by the union
of p-methoxyphenylethylamine and 3,4-methylene dioxy-
cinnamoyl chloride.
Ar m a ta m id e (N-(4′-m eth oxyp h en yl eth yl)-3, 4-m eth -
ylen ed ioxy cin n a m oyl a m id e) (1): white crystals; mp
-159.4 °C, Rf 0.7 (1% MeOH in CHCl3 with 5 drops of
This is the first report of the presence of a trans-
cinnamoylamide in Z. armatum. The isolation of these type
of amides in Zanthoxylum species is of chemotaxonomic
importance, as structurally related alkaloids have been
reported earlier from Zanthoxylum rubescens and Zan-
thoxylum thomense.9-12
diethylamine) IR(KBr) υ
3309, 1666-1668, 1623, 1617,
max
1586, 1447, 933 cm-1; UV λmax (MeOH) 202, 226, 288, and 320
nm; EIMS m/z 325 [M]+ (31), 190 [M - C9H11O]+ (51), 175 [M
- C9H12ON]+ (100, 148 [M - C9H8O2]+ (11), 145 (25), 134 [M
- C10H8O3N - H]+ (92), 121 [M - C11H10O3N]+ (30), 117 (18),
89 (35), 77 (7), 63 (10).
1H NMR (CDCl3) δ 2.78 (2H, t, J ) 6.9 Hz, H-11), 3.58 (2H,
q, J ) 6.9 Hz, H-10), 3.80 (3H, s, H-12), 6.00 (2H, s, H-13),
6.16 (1H, d, J ) 15.5 Hz, H-8), 7.50 (1H, d, J ) 15.5 Hz, H-7),
6.80-7.06 (2H, m, H-aromatic), 6.70-6.92 (4H, m, H-aromat-
ic); 13C NMR (CDCl3) δ 35.08 (C-11), 41.04 (C-10), 55.45 (C-
* To whom correspondence should be addressed.
† IHBT Communication no. 9816.
‡ Regional Research Laboratory Branch Office, Bundla Palampur - 176
061 (H. P.).
10.1021/np980224j CCC: $18.00
© 1999 American Chemical Society and American Society of Pharmacognosy
Published on Web 01/21/1999

312 J ournal of Natural Products, 1999, Vol. 62, No. 2
Notes
12), 101.36 (C-13), 106.58 (C-3′), 107.87 (C-2′)*, 108.18 (C-2)*,
109.01 (C-5′), 114.28 (C-5), 119.58 (C-6′), 124.27 (C-6), 126.36
(C-1′), 129.79 (C-8), 130.81 (C-1), 140.91 (C-7), 146.96 (C-4′),
148.96 (C-3), 151.74 (C-4), 163.60 (C-9), assignments bearing
an asterisk may be interchanged.
thank Dr. S. K. Banerjee, Chairman, Chemistry Section and
Dr. K. L. Dhar Emeritus Scientist, RRL, J ammu and Prof. C.
S. Pande, Emeritus Scientist, H.P. University, Shimla, for their
valuable discussions during the course of this study.
Syn th esis of N-(4′-m eth oxyp h en yl eth yl)-3, 4-m eth yl-
en ed ioxy cin n a m oyl a m id e (1). 3,4-Methylenedioxy cin-
namic acid (3.84 g, 0.02 mol) was refluxed with redistilled
thionyl chloride (1.8 mL., 0.025 mol) for 30 min to yield 3,4-
methylenedioxy cinnamoyl chloride in 62% yield. 4-Methoxy-
â-nitrostyrene (12.5 g) dissolved in 100 mL HOAc containg 5%
HCl was hydrogenated in the presence of 10% Pd-charcoal (1%)
for 1 h. After usual workup procedure, it yielded p-methoxy-
phenylethylamine (8.9 g, 71%). p-Methoxyphenylethylamine
(0.75 g, 0.005 mol) was taken in a mixture of dry C6H6 and
pyridine (1 mL each) and stirred with 3,4-methylenedioxy
cinnamoyl chloride (1.05 g, 0.005 mol) for two h. The solvent
was removed in vacuo. The gummy mass (1.63 g) thus obtained
was purified with hexane and EtOAc to furnish the compound
1 (210 mg). The product prepared exhibited spectral and
analytical data identical to the natural product.
Refer en ces a n d Notes
(1) The Wealth of India: Raw Materials; PID, Council of Scietific and
Industial Research (CSIR): New Delhi, 1976; Vol. II, pp 18-19.
(2) Despande, V. H.; Shastri, R. K. Indian J . Chem. 1977, 15B, 95.
(3) Nair, A. G. R.; Nair, G. A.; J oshua, C. P. Phytochemistry 1982, 21,
483-485.
(4) Muller, J . C.; Ourisson, G. Phytochemistry 1974, 13, 1615.
(5) Pelter, A. J . Chem. Soc. 1967, 1367.
(6) Heerden, F. R. V.; Braudt, F. V.; Roux, D. G. Phytochemistry 1980,
19, 2125.
(7) Atta-ur-Rahman; Bhatti, M. K.; Akhtar, R.; Choudhary, M. I. Phy-
tochemistry 1992, 31, 2869-2872.
(8) Hussain, S. F.; Gozler, B.; Shamma, M.; Gozler, T. Phytochemistry
1982, 22, 2979-2980.
(9) Dadson, B. A.; Minta, A. J . Chem. Soc., Perkin Trans. 1 1976, 2, 146-
147.
(10) Simeray, J .; Chanmont, J . P.; Bevalot, E.; Vaquette, J . Phytochemistry
1985, 24 , 2720-2721.
(11) Adesina, S. K. Planta Med. 1989, 55, 324-326.
(12) Adesina, S. K.; Reisch, J . Phytochemistry 1989, 28, 839-842.
Ack n ow led gm en t. We wish to record our thanks to the
Director, IHBT, Palampur for providing facilities. We also
NP980224J