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A Novel Cacalolide from Psacalium
Decompositum
Ricardo Reyes-Chilpa a , Manuel Jiménez-Estrada a , Marcia Godínez
b , Simón Hernández-Ortega a , María Campos c & Ezra Béjar d
a Instituto de Quimica, Universidad Nacional Autónoma de México,
Coyoacán, México, D.F., 04510
b San Diego State University, 5500 Campanile Dr. San Diego, CA,
92182-4616, U.S.
c Instituto Mexicano del Seguro Social, UIM Frmacología, Hospital
de Especialidades, CMN Siglo XXI, Av. Cuauhtémoc 330, México,
D.F., 06725
d Plant Bioassay™, 4153 Conrad Dr., Spring Valley, CA, 91977, U.S.
Version of record first published: 27 Oct 2010.
To cite this article: Ricardo Reyes-Chilpa, Manuel Jiménez-Estrada, Marcia Godínez, Simón
Hernández-Ortega, María Campos & Ezra Béjar (2002): A Novel Cacalolide from Psacalium
Decompositum, Natural Product Letters, 16:4, 239-242
To link to this article: http://dx.doi.org/10.1080/10575630290020532
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2. Natural Product Letters, Vol. 16, No. 4, pp. 239–242
A NOVEL CACALOLIDE FROM
PSACALIUM DECOMPOSITUM
RICARDO REYES-CHILPAa,*, MANUEL JIME´ NEZ-ESTRADAa,
MARCIA V. GODI´
NEZb, SIMO´
N HERNA ´
NDEZ-ORTEGAa,
MARI´A CAMPOSc and EZRA BE´
JARd
aInstituto de Quimica, Universidad Nacional Auto´noma de Me´xico. Coyoaca´n, 04510 Me´xico,
D.F.; bSan Diego State University, 5500 Campanile Dr. San Diego, CA 92182-4616, U.S.;
cUIM Frmacologı´a, Hospital de Especialidades, CMN Siglo XXI,
Instituto Mexicano del Seguro Social. Av. Cuauhte´moc 330, 06725, Me´xico, D.F.;
dPlant Bioassay2, 4153 Conrad Dr., Spring Valley, CA 91977, U.S.
(Received 12 December 2001; In final form 20 February 2002)
A new cacalolide sesquiterpenoid, named as Romo-A, was isolated from the roots of Psacalium decompositum,
Asteraceae, a Mexican medicinal shrub with antidiabetic properties. Its structure was elucidated by NMR,
MS, IR, UV, and confirmed by X-ray diffraction studies.
Keywords: Psacalium decompositum; Asteraceae; Cacalolides; Sesquiterpenoids; Furanoeremophilanes;
Diabetes mellitus
INTRODUCTION
Psacalium decompositum (A. Gray) H. Rob. and Brettell (Asteraceae) is a medicinal
shrub distributed in the mountains of Central and Northwestern Mexico. The roots
are sold in herbal markets and referred with the common name of ‘‘Matarique’’.
Traditional Tarahumaran, Yaqui and Pima practitioners in the Mexican states of
Sonora, Sinaloa and Chihuahua, prepare a water decoction of the roots of this or
other Psacalium species and give it to patients for the treatment of diabetes mellitus
and other ailments [1,2]. The traditional remedy, as well as the freeze dried water decoc-tion,
have been tested in several animal models, including alloxan diabetic mice, demon-strating
to lower blood glucose levels [3–5]. Several sesquiterpenoid components, such
as the cacalolides (biogenetic rearrangement products derived from furanoeremo-philanes
[6]), cacalol, cacalone, and epicacalone have been previously isolated from
Psacalium decompositum and related species [7–9]. A recent patent has been issued to
use these chemicals formulated either alone or in combination with sulfonylureas
and biguanides for the treatment of diabetes mellitus [10,11]. While re-isolating
*Corresponding author.
ISSN 1057-5634 print: ISSN 1029-2349 online 2002 Taylor Francis Ltd
DOI: 10.1080/10575630290020532
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3. 240 R. REYES-CHILPA et al.
major components from P. decompositum roots for testing their pharmacological prop-erties,
we have found occasionally some minor components not yet described, such as
hydroperoxycacalone [12]. In this occasion, we report a new minor cacalolide from this
source, which we named as Romo-A (1) to honor the late Dr. Jesu´ s Romo Armeria,
who initiated the chemical studies of this species.
RESULTS AND DISCUSSION
Compound 1 was obtained as a crystalline solid. Its IR spectrum showed absorption
bands at 1727 and 1668 cm1 indicating ester and conjugated carbonyl groups, respect-ively.
The UV spectrum was consistent with a quinone moiety, which was also sup-ported
by the 13C-NMR spectrum. Signals for two carbonyls were evident at 183.4
and 173.4, and were assigned to C-4 and C-9, respectively (Table I).
One carbonyl carbon belonging to an ester group was also noticed at 160.3 and
assigned to C-12. The 1H-NMR spectrum showed a wide singlet as 8.16 (1H) for
proton H-12 of a formic ester group. According to COSY, H-12 is coupled with
both H-10 methylene protons at 5.47 (t, J¼0.9 Hz, 2H). The low field chemical
shifts exhibited by H-10 and C-10 ( 55.82) also suggested this carbon is adjacent to
the formic ester group. A triplet at 7.79 (t, J¼0.9 Hz, 2H) suggested a vynilic
proton on a furano moiety, and was assigned to H-2. COSY indicated this proton is
also coupled with both H-10 methylene protons. Signals for three aromatic protons
( 7.54 dd, 7.61 t, and 8.16 dd) were assigned to H-6, H-7 and H-8 respectively,
while a singlet at 2.81 (s, 3H) suggested the aromatic ring is substituted with a
TABLE I 13C- and 1H-NMR Data for Romo A (1)
13C 1H (Hz) 13C 1H (Hz)
2 147.1 7.79 t (0.9), 1H 8 125.9 8.16 dd (1.5 and 7.5), 1H
3 128.4 – 8a 142.2 –
3a 120.7 – 9 173.4 –
4 183.4 – 9a 152.0 –
4a 130.3 – 10 55.8 5.47 t (0.9), 2H
5 133.8 – 12 160.3 8.16 s wide, 1H
6 138.4 7.54 dd (1.5 and 7.5), 1H 13 23.0 2.81 s, 3H
7 132.1 7.61 t (7.5), 1H
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4. CACALOLIDE FROM PSACALIUM DECOMPOSITUM 241
FIGURE 1 ORTEP projection of Romo-A.
methyl group. Assignment of all carbons is provided in Table I, and was deduced with
the aid of HMQC and HMBC experiments. HMBC showed long range coupling
between C-10 and H-12 indicating the formic ester location. It also showed the inter-action
between the C-9 (quinone carbonyl group) with H-8 on the aromatic ring, as
well as between C-3a and C-9a with H-2 on the furano ring. The EMIE spectrum exhib-ited
the Mþ at m/z 270 congruent with the molecular formula C15H10O5. It also exhib-ited
a fragment ion at m/z 241 (Mþ29) due to loss of H–C¼O. The parent ion of m/z
224 could be attributed to Mþ-HCOOH rupture. A monocrystal of 1 was obtained, and
the proposed structure was confirmed by X-ray diffraction studies (Fig. 1).
The crystal is constituted by three rings. The naphtoquinone frame is practically
planar (mean deviation 0.0071A ˚
), and the furano fragment has a dihedral angle of
1 with respect to the anterior frame. The formiate (O11–C12–O3) fragment make
a dihedral angle of 15.9 and 15 with napthoquinone and furano frames, respectively.
The unit cell has two molecules different crystallographically, they are joined by
hydrogen intermolecular bonds C22–H22 O5, (D–H 0.93 (1)A˚ , H–A 2.348 (3)A˚ ,
D–H–A 174.2(3). Molecules in the crystal are linked by intermolecular hydrogen
bonds C2–H2 – O4 (D–H 0.93 (1)A˚ , H–A 2.360(3)A˚ , D–H–A 176.5(3) symmetry
code xþ1, y, z) along XY plane and stacked along Z axis. Compound 1 has been pre-viously
obtained from dimaturin by chromium trioxide oxidation [8]. Nevertheless, this
is the first time it is found as a natural product.
EXPERIMENTAL
Plant Material
Psacalium decompositum roots were purchased at the Sonora Market, in Mexico City.
The specimen was authenticatd by Dr. Abigail Aguilar and a voucher specimen was
deposited in the IMSSM Herbarium in Mexico City.
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5. 242 R. REYES-CHILPA et al.
Isolation
The roots (962.68 g) were exhaustively extracted with CH2Cl2 (33 L) and the solvent
evaporated in vacuo. A red-brown gummy extract was obtained (47.78 g, 4.8%) and
macerated with hexane to remove cacalol. The remaining CH2Cl2 extract (45.5 g) was
subjected to column chromatography (1,365 g of SiO2 desiccant, grade 922, mesh size
200325 CF 0.85 from Davison Chemical, Baltimore 3, Maryland Grace). All frac-tions
were analyzed by TLC (Silica gel, GFD-254, Merck), using as general spray
Cerium Sulfate reagent followed by mild heat. Fractions eluted with hexane–CH2Cl2
(50 : 50) afforded cacalol, while those eluted with CH2Cl2 (100%) yielded compound
1 (35 mg).
Romo-A (1) was obtained as amber needles (CH2Cl2): mp 168–170C; UV (CH3CN)
max () 246 (32473), 289 (6689), 350 (5067) nm; IR (CHCl3) max 1727, 1688,
1587 cm1; 1H-NMR (CDCl3, 300MHz): see Table I, 13C-NMR (CDCl3, 75 MHz):
see Table I; EIMS m/z 270 [Mþ] (20), 241 [Mþ-HCO] (4), 224 [Mþ-HCOOH] (100),
196 [224-H2O] (9), 168 (7), 140 (7), 139 (14), 128 (6), 115 (5), 89 (6), 69 (5), 57 (6), 43
(5), 41 (3); anal. C 66.57%, H 3.77%, Calculated for C15H10O5, C 66.57%, H 3.7%,
O 29.62%. Crystallographic data for the structure reported in this paper has been
deposited with the Cambridge Crystallographic Data Center. Copies of the data can
be obtained as supplementary publication CCDC-164214, free of charge on application
to the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: þ44-(0) 1223-
336033 or E-mail: deposit@ccdc.cam.ac.uk.
Acknowledgments
We are grateful with Gabriela Flores Arredondo for laboratory assistance, and with
Beatriz Quiroz, Isabel Chavez, He´ctor Rios, Luis Velasco, Javier Pe´rez, and Rocio
Patin˜ o, for recording the NMR, MS, IR and UV spectra. Dr. Abigail Aguilar kindly
identified P. decompositum sample. Marcia V. Godı´nez was supported by a grant
provided by the SDSU/UCSD Minority International Research Training (MIRT)
program of the Fogarty International, National Institute of Health, U.S.A.
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