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An eudesmanolide and a carotane from Ferula sinaica
Phytochemistry 57 (2001) 513–515 www.elsevier.com/locate/phytochem
An eudesmanolide and a carotane from Ferula sinaica Ahmed A. Ahmeda,*, Mohamed H. Abdel-Razekb, Mahmoud I. Nassarc, Shunsuke Izumib, Sinji Ohtad, Toshifumi Hiratab a Department of Chemistry, Faculty of Science, El-Minia University, El-Minia, Egypt Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan c Natural Products Chemistry Department, National Research Centre, Dokki, Cairo, Egypt d Instrumental Center for Chemical Analysis, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan b
Received in revised form 8 November 2000; accepted 6 March 2001
Abstract Re-examination of the chemical constituents of the leaves of Ferula sinaica afforded a new eudesmanolide and a new carotane. The structures were elucidated by spectroscopic methods. # 2001 Elsevier Science Ltd. All rights reserved. Keywords: Ferula sinaica; Apiaceae; Sesquiterpenes; Eudesmanolide; Carotane
1. Introduction Ferula sinaica L. (Apiaceae) is widespread on Sinai peninsula, Egypt and its resin has been used in folk medicine for treatment of various diseases (Boulos, 1983). Chemically, the resin of the species is characterized by the presence of sesquiterpenes, sesquiterpene coumarins and monoterpenes (Al-Hazimi, 1986; Ahmed, 1990, 1991, 1999). A previous investigation of the leaves of F. sinaica has revealed the presence of a glucose derivative and 2C-methyl-d-erythritol (Ahmed et al., 1996). We report here the isolation and characterization of a new carotane and a rare eudesmanolide constituent from the leaves of F. sinaica. Few eudesmanolides have been reported from the genus Ferula (Gonzalez and Barrera, 1995).
2. Results and discussion Fractionation of the dichloromethane–methanol (1:1) extracts of the leaves of F. sinaica by column chromatography on silica gel and on Sephadex LH-20 gave a new eudesmanolide 1 and a new carotane 2.
* Corresponding author. Tel.: +20-86-345-267; fax: 20-86-342-601. E-mail address: [email protected] (A.A. Ahmed).
The spectral data of compound 1 suggested a different skeleton type than those which are common in the genus Ferula. 1H NMR spectrum of 1, in pyridine-d5, displayed three methyl signals at 1.13, 1.15 and 1.47, two being due to two tertiary methyls and two protons geminal to hydroxyl groups were observed at 4.90 (J= 6.5, 9.5 Hz) and 3.60 (J=4, 11 Hz). The downfield shift of the signal at 4.90 suggested the oxygen function at C-6 could be acylated or lactonized. This proton showed a correlation with a narrow doublet at 1.86 and a multiplet at 2.58 in the 1H–1H COSY. Additionally, a methyl doublet at 1.15 was correlated with a multiplet signal at 2.82 which itself correlated with the multiplet at 2.58. These data could be assigned to a a-methyl-g-lactone moiety. The double doublet at 3.60 (J= 4, 11 Hz) was characteristic for a proton geminal to equatorial hydroxyl group at C-3. The 13C NMR spectrum of compound 1, in CDCl3, exhibited 15 nonequivalent carbon atoms. The assignment of the carbon signals was established from DEPT and HMQC experiments. This data suggested the presence of an eudesmanolide structure, a rare constituents in the genus Ferula (Gonzalez and Barrera, 1995). Although, the coupling constant suggested the stereochemistry of H-3, H-5 and H-6, NOESY experiment, in pyridine-d5, supported the proposed stereochemistry. H-6 showed a cross-peak with H-7, H-14 and H-15. While, H-7 exhibited a crosspeak with H-14 and H-11; H-5 showed a correlation
0031-9422/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S0031-9422(01)00115-7
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A.A. Ahmed et al. / Phytochemistry 57 (2001) 513–515
with H-3. HREI mass spectrum afforded a molecular ion peak at m/z 268.1660, C15H24O4. Therefore, compound 1 has the structure of a 3 ,4 -dihydroxy-5 H, 11 H-eudesman-6,12-olide. Of similar structure related compounds, one has been synthesized and showed cell growth inhibitory activity against lymphocytic leukemia (P-388) in vitro (Ando et al., 1991), the second was a biotransformation products (Amate et al., 1991). The structure of compound 2 could be easily established by comparison of its spectral data with those of lancerotriol derivatives (Fraga et al., 1985, 1986; Garg et al., 1987; El-Sayed, 1990; Miski and Jakupovic,
Table 1 1 H NMR of compounds 1, 2 and 2a (400 MHz, CDCl3) Protons
1b
1c
H-1a H-1b H-2a H-2b H-3a H-3b H-5 H-6 H-7 H-8a H-8b H-9a H-9b H-10a H-10b H-11 H-12 H-13 H-14 H-15 30 , 70 40 , 60 AcO
1.55 m 1.55 m 1.50 m 1.65 3.45 dd (4.0, 11.0)a – 1.60 d (9.5) 4.85 dd (6.5, 9.5) 2.75 m 1.50 m 1.65 m 1.60 m 1.75 m – – – – 2.80 m – – 1.25 d (7.0) 0.90 s 1.35 s
1.24 1.45 1.80
a b c
2
1.86 4.90 2.58 1.23 1.44 1.95 1.85
2.82 1.15 1.13 1.47
J values (Hz) are given in parentheses. Assigned by 1H and 1H–13C COSY. In pyridine-d5.
2a
1.30 1.60 1.80
3.60 2.20 d (10.0) 5.87 d (10.0) 5.40 br s
2.22 5.91 5.40
5.57 m
5.50
1.88 qq (7,7) 0.90 d (7.0) 0.80 d (7.0) 1.73 s 1.22 s 7.85 d (8.5) 6.82 d (8.5) 2.05 s
1990). An additional sharp singlet signal, integrated for three protons appeared at 2.05 and could be assigned to an acetyl group. The chemical shift of H-9 as a multiplet at downfield ( 5.57), compare to H-9 of lancerotriol 6-vanillate ( 4.30) indicated the presence of an acetyl group at C-9. The second acyl group was established as p-hydroxybenzoate from the 1H and 13C NMR (Tables 1 and 2). The other 1H and 13C signals were very close to those of lancerotriol derivatives. The HRCI mass spectrum afforded a molecular ion at m/z 417.2251 (calc. 417.2277, C24H32O6). Acetylation of 2 gave the acetyl product 2a. Its 1H and 13C NMR data are reported in Tables 1 and 2. Moreover, the configuration at C9 was supported from NOE experiment. Irradiation of H-14 of 2a enhanced H-6 and H-9.
2.00 1.60 1.72 0.98 0.82 1.75 1.23 8.07 7.19 2.08 2.33
Table 2 13 C NMR of compounds 1, 2 and 2a (100 MHz, CDCl3, values) Carbons
1
C-1 C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-11 C-12 C-13 C-14 C-15 C-10 C-20 C-30 , 70 C-40 , 60 C-50 AcO
37.3 18.4 79.9 71.6 51.8 79.0 36.2 28.3 39.1 37.9 37.2 178.4 11.4 16.3 24.4
2 t t d s d d d t t s d s q q q
42.1 41.6 31.5 86.5 54.6 72.4 127.7 135.6 72.0 46.3 36.7 17.3 18.2 23.5 18.7 166.4 121.7 131.9 115.3 161.0 170.2 21.0
2a s t t s d d d s d t d q q q q s s d d s s q
42.0 41.6 31.6 86.2 54.5 71.8 127.4 135.8 72.9 46.2 36.8 17.2 18.2 23.5 18.7 166.1 127.6 131.2 121.6 154.3 170.3, 168.7 21.0, 21.0
A.A. Ahmed et al. / Phytochemistry 57 (2001) 513–515
3. Experimental 3.1. Plant material Leaves of F. sinaica were collected from North Sinai peninsula, El-Arish, Egypt, in March 1997 by one of us (AAA). A voucher specimen (AAA 110) is deposited in the department of Botany, El-Minia University, Egypt. 3.2. Extraction Air-dried leaves of F. sinaica (500 g) were extracted with MeOH–CH2Cl2 (1:1). The extract was defatted and chromatographed on Si gel column packed into petroleum ether (bp 40–60 C) and eluted with a petroleum ether– Et2O step gradient. The fractions eluted with petroleum ether–Et2O (1:1 and 1:2) were combined and further chromatographed on a Sephadex LH-20 column with an initial solvent of Et2O–CH2Cl2–MeOH (7:4:0.5) to give 9 mg of 1, and 11 mg of 2. 3.3. Physical and spectral data 3.3.1. 3 ,4 -Dihydroxy-5 H, 11 H-eudesman-6,12olide (1) IR max CHCl3 cm1: 3510, 3425, 1785. HREIMS m/z (rel. int): 268.1660 [M]+ (45) (calc. 268.1675); molecular formula: C15H24O4. 3.3.2. Lancerotriol 9-acetate-6-p-hydroxybenzoate (2) IR max CHCl3 cm1: 3445, 2975, 2885, 1700, 1690. HRCIMS m/z (rel. int.): 417.2251 [M+H]+ (calc. 417.2277, C24H32O6), 399.2170 [M+H–H2O]+ (100) (Calc. 399.2171); molecular formula: C24H30O5. Acetylation of 2: 8 mg of 2 was heated with Ac2O in pyridine, at 70 C for 1 h. The mixture was decomposed by distilled water and was extracted with CH2Cl2. The organic layer was concentrated and purified by Sephadex LH-20 column (n-hexane–CH2Cl2–MeOH, 8:3:0.5) to give 6 mg of 2a. IR max CHCl3 cm1: 2890, 2885, 1695,
515
1690. HRCIMS m/z (rel. int.): 459.2367 [M+H]+ (11) (calc. 459.2383, C26H34O7), 441.2275 [M+H–H2O]+(100) (calc. 441.2278); molecular formula: C26H32O6.
References Ahmed, A.A., 1990. New sesquiterpenes from Ferula sinaica. Journal of Natural Products 53, 483–486. Ahmed, A.A., 1991. Daucanes and other constituents from Ferula sinaica. Phytochemistry 30, 1207–1210. Ahmed, A.A., 1999. Sesquiterpene coumarins and sesquiterpenes from Ferula sinaica. Phytochemistry 50, 109–112. Ahmed, A.A., Abdel-Razek, M.H., Abu-Mustafa, E.A., Williams, H.J., Scott, A.I., Reibenspies, J.H., Mabry, T.J., 1996. A new derivative of glucose and 2-C-methyl-d-erythritol from Ferula sinaica. Journal of Natural Products 59, 1171–1173. Al-Hazimi, H.M., 1986. Terpenoids and a coumarin from Ferula sinaica. Phytochemistry 25, 2417–2419. Amate, Y., Granados, A.G., Martı´nez, A., Buruaga, A.S., Breto´n, J.L., Onorato, M.E., Arias, J.M., 1991. Biotransformation of 6beudesmanolides functionolized at C-3 with Curvularia lunata and Rhizoupus nigricans cultures. Tetrahedron 47, 5811–5818. Ando, M., Isogal, K., Azami, H., Hirata, N., Yanagi, Y., 1991. Studies on the synthesis of sesquiterpene lactones, 12. Synthesis of (+)colartin, (+)-arbasculin A and their C-4 epimers and their biological activities. Journal Natural Products 54, 1017–1024. Boulos, L., 1983. Medicinal Plants of North Africa. Algonac, MI. El-Sayed, N.H., 1990. Carotane sesquiterpene from Ferula sinaica. Pharmazie 45, 538. Fraga, B.M., Hernandez, M.G., Diaz, J.G., Gonzalez, A.G., Gonzalez, P., 1986. Carotane sesquiterpene from Ferula linkii. Phytochemistry 25, 2883–2886. Fraga, B.M., Gonzaˆlez, A.G., Gonzaˆlez, P., Hernandez, M.G., Larruga, C.L., 1985. Carotane sesquiterpene from Ferula lancerottensis. Phytochemistry 29, 501–504. Garg, S.N., Agarwal, S.K., Mahajan, V.P., Rastogi, S.N., 1987. Feruginidin and ferugin, two new sesquiterpenoids based on the carotane skeleton from Ferula jaeschkeana. Journal of Natural Products 50, 253–255. Gonzalez, A.G., Barrera, B., 1995. Chemistry and sources of monoand bicyclic sesquiterpenes from Ferula species. Progress in Chemistry of Organic Natural Products 64, 1–92. Miski, M., Jakupovic, J., 1990. Daucane esters from Ferula rigidula. Phytochemistry 29, 173–178.
An eudesmanolide and a carotane from Ferula sinaica Ahmed A. Ahmeda,*, Mohamed H. Abdel-Razekb, Mahmoud I. Nassarc, Shunsuke Izumib, Sinji Ohtad, Toshifumi Hiratab a Department of Chemistry, Faculty of Science, El-Minia University, El-Minia, Egypt Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan c Natural Products Chemistry Department, National Research Centre, Dokki, Cairo, Egypt d Instrumental Center for Chemical Analysis, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan b
Received in revised form 8 November 2000; accepted 6 March 2001
Abstract Re-examination of the chemical constituents of the leaves of Ferula sinaica afforded a new eudesmanolide and a new carotane. The structures were elucidated by spectroscopic methods. # 2001 Elsevier Science Ltd. All rights reserved. Keywords: Ferula sinaica; Apiaceae; Sesquiterpenes; Eudesmanolide; Carotane
1. Introduction Ferula sinaica L. (Apiaceae) is widespread on Sinai peninsula, Egypt and its resin has been used in folk medicine for treatment of various diseases (Boulos, 1983). Chemically, the resin of the species is characterized by the presence of sesquiterpenes, sesquiterpene coumarins and monoterpenes (Al-Hazimi, 1986; Ahmed, 1990, 1991, 1999). A previous investigation of the leaves of F. sinaica has revealed the presence of a glucose derivative and 2C-methyl-d-erythritol (Ahmed et al., 1996). We report here the isolation and characterization of a new carotane and a rare eudesmanolide constituent from the leaves of F. sinaica. Few eudesmanolides have been reported from the genus Ferula (Gonzalez and Barrera, 1995).
2. Results and discussion Fractionation of the dichloromethane–methanol (1:1) extracts of the leaves of F. sinaica by column chromatography on silica gel and on Sephadex LH-20 gave a new eudesmanolide 1 and a new carotane 2.
* Corresponding author. Tel.: +20-86-345-267; fax: 20-86-342-601. E-mail address: [email protected] (A.A. Ahmed).
The spectral data of compound 1 suggested a different skeleton type than those which are common in the genus Ferula. 1H NMR spectrum of 1, in pyridine-d5, displayed three methyl signals at 1.13, 1.15 and 1.47, two being due to two tertiary methyls and two protons geminal to hydroxyl groups were observed at 4.90 (J= 6.5, 9.5 Hz) and 3.60 (J=4, 11 Hz). The downfield shift of the signal at 4.90 suggested the oxygen function at C-6 could be acylated or lactonized. This proton showed a correlation with a narrow doublet at 1.86 and a multiplet at 2.58 in the 1H–1H COSY. Additionally, a methyl doublet at 1.15 was correlated with a multiplet signal at 2.82 which itself correlated with the multiplet at 2.58. These data could be assigned to a a-methyl-g-lactone moiety. The double doublet at 3.60 (J= 4, 11 Hz) was characteristic for a proton geminal to equatorial hydroxyl group at C-3. The 13C NMR spectrum of compound 1, in CDCl3, exhibited 15 nonequivalent carbon atoms. The assignment of the carbon signals was established from DEPT and HMQC experiments. This data suggested the presence of an eudesmanolide structure, a rare constituents in the genus Ferula (Gonzalez and Barrera, 1995). Although, the coupling constant suggested the stereochemistry of H-3, H-5 and H-6, NOESY experiment, in pyridine-d5, supported the proposed stereochemistry. H-6 showed a cross-peak with H-7, H-14 and H-15. While, H-7 exhibited a crosspeak with H-14 and H-11; H-5 showed a correlation
0031-9422/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S0031-9422(01)00115-7
514
A.A. Ahmed et al. / Phytochemistry 57 (2001) 513–515
with H-3. HREI mass spectrum afforded a molecular ion peak at m/z 268.1660, C15H24O4. Therefore, compound 1 has the structure of a 3 ,4 -dihydroxy-5 H, 11 H-eudesman-6,12-olide. Of similar structure related compounds, one has been synthesized and showed cell growth inhibitory activity against lymphocytic leukemia (P-388) in vitro (Ando et al., 1991), the second was a biotransformation products (Amate et al., 1991). The structure of compound 2 could be easily established by comparison of its spectral data with those of lancerotriol derivatives (Fraga et al., 1985, 1986; Garg et al., 1987; El-Sayed, 1990; Miski and Jakupovic,
Table 1 1 H NMR of compounds 1, 2 and 2a (400 MHz, CDCl3) Protons
1b
1c
H-1a H-1b H-2a H-2b H-3a H-3b H-5 H-6 H-7 H-8a H-8b H-9a H-9b H-10a H-10b H-11 H-12 H-13 H-14 H-15 30 , 70 40 , 60 AcO
1.55 m 1.55 m 1.50 m 1.65 3.45 dd (4.0, 11.0)a – 1.60 d (9.5) 4.85 dd (6.5, 9.5) 2.75 m 1.50 m 1.65 m 1.60 m 1.75 m – – – – 2.80 m – – 1.25 d (7.0) 0.90 s 1.35 s
1.24 1.45 1.80
a b c
2
1.86 4.90 2.58 1.23 1.44 1.95 1.85
2.82 1.15 1.13 1.47
J values (Hz) are given in parentheses. Assigned by 1H and 1H–13C COSY. In pyridine-d5.
2a
1.30 1.60 1.80
3.60 2.20 d (10.0) 5.87 d (10.0) 5.40 br s
2.22 5.91 5.40
5.57 m
5.50
1.88 qq (7,7) 0.90 d (7.0) 0.80 d (7.0) 1.73 s 1.22 s 7.85 d (8.5) 6.82 d (8.5) 2.05 s
1990). An additional sharp singlet signal, integrated for three protons appeared at 2.05 and could be assigned to an acetyl group. The chemical shift of H-9 as a multiplet at downfield ( 5.57), compare to H-9 of lancerotriol 6-vanillate ( 4.30) indicated the presence of an acetyl group at C-9. The second acyl group was established as p-hydroxybenzoate from the 1H and 13C NMR (Tables 1 and 2). The other 1H and 13C signals were very close to those of lancerotriol derivatives. The HRCI mass spectrum afforded a molecular ion at m/z 417.2251 (calc. 417.2277, C24H32O6). Acetylation of 2 gave the acetyl product 2a. Its 1H and 13C NMR data are reported in Tables 1 and 2. Moreover, the configuration at C9 was supported from NOE experiment. Irradiation of H-14 of 2a enhanced H-6 and H-9.
2.00 1.60 1.72 0.98 0.82 1.75 1.23 8.07 7.19 2.08 2.33
Table 2 13 C NMR of compounds 1, 2 and 2a (100 MHz, CDCl3, values) Carbons
1
C-1 C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-11 C-12 C-13 C-14 C-15 C-10 C-20 C-30 , 70 C-40 , 60 C-50 AcO
37.3 18.4 79.9 71.6 51.8 79.0 36.2 28.3 39.1 37.9 37.2 178.4 11.4 16.3 24.4
2 t t d s d d d t t s d s q q q
42.1 41.6 31.5 86.5 54.6 72.4 127.7 135.6 72.0 46.3 36.7 17.3 18.2 23.5 18.7 166.4 121.7 131.9 115.3 161.0 170.2 21.0
2a s t t s d d d s d t d q q q q s s d d s s q
42.0 41.6 31.6 86.2 54.5 71.8 127.4 135.8 72.9 46.2 36.8 17.2 18.2 23.5 18.7 166.1 127.6 131.2 121.6 154.3 170.3, 168.7 21.0, 21.0
A.A. Ahmed et al. / Phytochemistry 57 (2001) 513–515
3. Experimental 3.1. Plant material Leaves of F. sinaica were collected from North Sinai peninsula, El-Arish, Egypt, in March 1997 by one of us (AAA). A voucher specimen (AAA 110) is deposited in the department of Botany, El-Minia University, Egypt. 3.2. Extraction Air-dried leaves of F. sinaica (500 g) were extracted with MeOH–CH2Cl2 (1:1). The extract was defatted and chromatographed on Si gel column packed into petroleum ether (bp 40–60 C) and eluted with a petroleum ether– Et2O step gradient. The fractions eluted with petroleum ether–Et2O (1:1 and 1:2) were combined and further chromatographed on a Sephadex LH-20 column with an initial solvent of Et2O–CH2Cl2–MeOH (7:4:0.5) to give 9 mg of 1, and 11 mg of 2. 3.3. Physical and spectral data 3.3.1. 3 ,4 -Dihydroxy-5 H, 11 H-eudesman-6,12olide (1) IR max CHCl3 cm1: 3510, 3425, 1785. HREIMS m/z (rel. int): 268.1660 [M]+ (45) (calc. 268.1675); molecular formula: C15H24O4. 3.3.2. Lancerotriol 9-acetate-6-p-hydroxybenzoate (2) IR max CHCl3 cm1: 3445, 2975, 2885, 1700, 1690. HRCIMS m/z (rel. int.): 417.2251 [M+H]+ (calc. 417.2277, C24H32O6), 399.2170 [M+H–H2O]+ (100) (Calc. 399.2171); molecular formula: C24H30O5. Acetylation of 2: 8 mg of 2 was heated with Ac2O in pyridine, at 70 C for 1 h. The mixture was decomposed by distilled water and was extracted with CH2Cl2. The organic layer was concentrated and purified by Sephadex LH-20 column (n-hexane–CH2Cl2–MeOH, 8:3:0.5) to give 6 mg of 2a. IR max CHCl3 cm1: 2890, 2885, 1695,
515
1690. HRCIMS m/z (rel. int.): 459.2367 [M+H]+ (11) (calc. 459.2383, C26H34O7), 441.2275 [M+H–H2O]+(100) (calc. 441.2278); molecular formula: C26H32O6.
References Ahmed, A.A., 1990. New sesquiterpenes from Ferula sinaica. Journal of Natural Products 53, 483–486. Ahmed, A.A., 1991. Daucanes and other constituents from Ferula sinaica. Phytochemistry 30, 1207–1210. Ahmed, A.A., 1999. Sesquiterpene coumarins and sesquiterpenes from Ferula sinaica. Phytochemistry 50, 109–112. Ahmed, A.A., Abdel-Razek, M.H., Abu-Mustafa, E.A., Williams, H.J., Scott, A.I., Reibenspies, J.H., Mabry, T.J., 1996. A new derivative of glucose and 2-C-methyl-d-erythritol from Ferula sinaica. Journal of Natural Products 59, 1171–1173. Al-Hazimi, H.M., 1986. Terpenoids and a coumarin from Ferula sinaica. Phytochemistry 25, 2417–2419. Amate, Y., Granados, A.G., Martı´nez, A., Buruaga, A.S., Breto´n, J.L., Onorato, M.E., Arias, J.M., 1991. Biotransformation of 6beudesmanolides functionolized at C-3 with Curvularia lunata and Rhizoupus nigricans cultures. Tetrahedron 47, 5811–5818. Ando, M., Isogal, K., Azami, H., Hirata, N., Yanagi, Y., 1991. Studies on the synthesis of sesquiterpene lactones, 12. Synthesis of (+)colartin, (+)-arbasculin A and their C-4 epimers and their biological activities. Journal Natural Products 54, 1017–1024. Boulos, L., 1983. Medicinal Plants of North Africa. Algonac, MI. El-Sayed, N.H., 1990. Carotane sesquiterpene from Ferula sinaica. Pharmazie 45, 538. Fraga, B.M., Hernandez, M.G., Diaz, J.G., Gonzalez, A.G., Gonzalez, P., 1986. Carotane sesquiterpene from Ferula linkii. Phytochemistry 25, 2883–2886. Fraga, B.M., Gonzaˆlez, A.G., Gonzaˆlez, P., Hernandez, M.G., Larruga, C.L., 1985. Carotane sesquiterpene from Ferula lancerottensis. Phytochemistry 29, 501–504. Garg, S.N., Agarwal, S.K., Mahajan, V.P., Rastogi, S.N., 1987. Feruginidin and ferugin, two new sesquiterpenoids based on the carotane skeleton from Ferula jaeschkeana. Journal of Natural Products 50, 253–255. Gonzalez, A.G., Barrera, B., 1995. Chemistry and sources of monoand bicyclic sesquiterpenes from Ferula species. Progress in Chemistry of Organic Natural Products 64, 1–92. Miski, M., Jakupovic, J., 1990. Daucane esters from Ferula rigidula. Phytochemistry 29, 173–178.