This Issue is Dedicated to Professor Werner Herz on the Occasion of his 90th Birthday Volume 5. Issue 5. Pages 667-840. 2010 ISSN 1934-578X (printed); ISSN 1555-9475 (online) www.naturalproduct.us
Natural Product Communications
EDITOR-IN-CHIEF DR. PAWAN K AGRAWAL Natural Product Inc. 7963, Anderson Park Lane, Westerville, Ohio 43081, USA
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PROFESSOR DEAN GUO State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China [email protected]
PROFESSOR J. ALBERTO MARCO Departamento de Quimica Organica, Universidade de Valencia, E-46100 Burjassot, Valencia, Spain [email protected]
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Natural Product Communications
Eudesmanolides and Methyl Ester Derivatives from Dimerostemma arnottii
2010 Vol. 5 No. 5 669 - 674
Sérgio Ricardo Ambrosioa, Ricardo Stefanib, Vladimir Constantino Gomes Helenoa, Márcio Antônio de Menezesa, Antonio Gilberto Ferreirac, Paulo Gustavo Barboni Dantas Nascimentod , Mara Angelina Galvão Magentae and Fernando Batista Da Costad,* a
Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, 14404-600, Franca, SP, Brazil b
Laboratório de Química Bio-Orgânica do Araguaia, Universidade Federal de Mato Grosso, 78698-000, Pontal do Araguaia, MT, Brazil
Departamento de Química, Universidade Federal de São Carlos, 13565-905, São Carlos, SP, Brazil
Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903, Ribeirão Preto, SP, Brazil e
Faculdade de Ciências Biológicas, Universidade Santa Cecília, UNISANTA, 11045-907, Santos, SP, Brazil
Received: December 1st, 2009; Accepted: March 10th, 2010 Dedicated to Professor Werner Herz on the occasion of his 90th birthday.
The phytochemical investigation of Dimerostemma arnottii (Asteraceae) afforded, in addition to a known eudesmanolide, two unusual eudesmane methyl ester derivatives and a new eudesmanolide. Structural elucidation of the compounds was based on their 1D and 2D NMR spectroscopic as well as HR-ESI-MS data. There is a remarkable similarity between the structures of the eudesmanes from D. arnottii and those previously encountered in other Dimerostemma species, which is in agreement with the results of a previous phylogenetic study based on molecular data. The chemotaxonomic relevance of the isolated compounds is briefly discussed. Keywords: Asteraceae, Heliantheae, eudesmanes, sesquiterpene lactones, Dimerostemma arnottii, Dimerostemma.
Dimerostemma Cass. (Asteraceae, tribe Heliantheae, subtribe Verbesininae sensu Bremer) is a genus with 29 species endemic in South America and concentrated mainly in midwestern Brazil . On the basis of a recent molecular phylogenetic study, the former genus Angelphytum was included in Dimerostemma. Conclusively, all species of Angelphytum were transferred to Dimmerostemma, and the former A. arnottii (Baker) H.Rob. is now named D. arnottii (Baker) M. D. Moraes. Only a few species of Dimmerostema have been chemically investigated so far, revealing a dominance of sesquiterpene lactones of the eudesmanolide subtype [2-6]. These eudesmanolides show an unusual substitution pattern that is not observed in any other genus .
As part of a continuing investigation of the chemical structures and biological activities of sesquiterpene lactones from Brazilian Asteraceae [2,7-10], we performed a phytochemical study of the dichloromethane extract of the leaves of D. arnottii. We report herein the isolation and structural elucidation of a new eudesmanolide (1) and two unusual methyl ester derivatives (2 and 4), as well as the isolation of the known dimerostemmolide 1-O-[2-methyl-2,3-epoxy butyrate] [4,11] (3, Figure 1). The structural elucidation of the four closely related compounds started with the already known eudesmanolide 3. This elucidation was carried out by comparison of the obtained NMR and ESI-MS data (not shown) with previously published data [4,11]. It is important to mention that the complete 1H NMR data
670 Natural Product Communications Vol. 5 (5) 2010
O O 2 3
1' 14 10 5
2 O O O
OH H 3 CO
OH H 3 CO
Figure 1: Eudesmanes isolated from the leaves of D. arnottii.
containing all individual coupling constant values and cleared multiplicities described in the present work (Table 1) are not available in the literature. Moreover, unpublished 2D correlations (Table 2) and 13C NMR data (Table 3) of 3 have also been obtained and are now being reported.
Ambrosio et al.
The NMR spectra of 4 were very similar to those of 3, but the 1H NMR data revealed significant differences in the chemical shifts of the protons at positions 5-9 and 13 (Table 1), while in the 13C NMR spectra such differences occurred at positions 7-9, 12, and 13 (Table 3). Together with this information, an extra signal at δ 51.8 in the 13C NMR spectrum and a 3H singlet at δ 3.74 in the 1H NMR spectrum of 4 have led us to propose the methyl ester moiety at C12, which is shown in Figure 1. Confirmation of this was achieved with the aid of HMBC data, which showed the correlations between C12 and H16, as well as C5, C6, and C7 with the hydrogen atom of the C6-hydroxyl group (Table 2). The assignment of the NMR signals of the epoxyangelate at C1 and analysis of HR-ESI-MS data confirmed the structure of 4 as a new eudesmane methyl ester. Besides the ester moiety, the signals of H3b, H15a, and H15b in the 1H NMR spectrum of 1 are significantly different when compared with those of 3 (Table 1). The differences in the chemical shifts of C4 (δ 144.4) and C15 (δ 109.3) in the 13C NMR data (Table 3) were also
Table 1: 1H NMR spectroscopic data for compounds 1 to 4 (400 MHz, CDCl3). 1 4.82 (1H, dd, J1/2a=2.1, J1/2b=2.5) 1.95 (1H, dddd,J2a/1=2.1, J2a/3a=5.7, J2a/3b=14.3, J2a/2b=14.4)
δH in ppm (integral, multiplicity) J in Hz 2 3 4.60 (1H, dd, J1/2a=2.3, J1/2b=2.50 4.82 (1H, dd, J1/2b=2.4, J1/2a=2.6) 1.89 (1H, dddd, J2a/1=2.3, J2a/3a=5.8, 2.06 (1H, dddd, J2a/1=2.6, J2a/3b=4.8, J2a/3b=13.1, J2a/2b=14.1) J2a/3a=14.2, J2a/2b=15.3)
4 4.74 (1H, dd, J1/2b=2.2, J1/2a=2.5) 2.03 (1H, dddd, J2a/1=2.5, J2a/3b=4.3, J2a/3a=14.5, J2a/2b=15.0)
1.75 (1H, dddd, J2b/1=2.5, J2b/3b=4.9, J2b/3a=13.5, J2b/2a=14.4)
1.80 (1H, dddd, J2b/3a=1.6, J2b/1=2.5, J2b/3b=5.2, J2b/2a=14.1)
1.93 (1H, dddd, J2b/3b=1.7, J2b/1=2.4, J2b/3a=5.3, J2b/2a=15.3)
1.87 (1H, dddd, J2b/3b=2.0, J2b/1=2.2, J2b/3a=4.2, J2b/2a=15.0)
2.29 (1H, ddd, J3a/2a=5.7, J3a/3b=13.2, J3a/2b=13.5)
2.21 (1H, ddd, J3a/2b=1.6, J3a/2a=5.8, J3a/3b=13.4)
2.22 (1H, dddd, J3a/15a=1.8, J3a/2b=5.3, J3a/3b=13.2, J3a/2a=14.2)
2.20 (1H, dddd, J3a/15a=1.5, J3a/2b=4.2, J3a/3b=13.0, J3a/2a=14.5)
2.23 (1H, ddd, J3b/2b=4.9, J3b/3a=13.2, J3b/2a=14.3) 2.39 (1H, d, J5/6=9.7)
2.16 (1H, ddd, J3b/2b=5.2, J3b/2a=13.1, J3b/3a=13.4) 2.28 (1H, d, J5/6=10.2)
1.26 (1H, ddd, J3b/2b=1.7, J3b/2a=4.8, J3b/3a=13.2) 2.42 (1H, d, J5/6=9.7)
1.19 (1H, ddd, J3b/2b=2.0, J3b/2a=4.3, J3b/3a=13.0) 2.23 (1H, d, J5/6=10.2)
4.04 (1H, dd, J6/5=9.7, J6/7=9.9)
4.10 (1H, t, J6/5=J6/7=10.2)
3.87 (1H, t, J6/5=J6/7=9.7)
3.96 (1H, t, J6/5=J6/7=10.2)
2.54 (1H, dddd, J7/13b=2.8, J7/13a=3.1, J7/6=9.9, J7/8=10.9)
2.32 (1H, t, J7/6=J7/8=10.2)
2.51 (1H, dddd, J7/13b=2.6, J7/13a=3.0, J7/6=9.7, J7/8=11.5)
2.25 (1H, dd, J7/8=10.0, J7/6=10.2)
3.89 (1H, ddd, J8/9a=3.6, J8/7=10.9, J8/9b=11.6) 1.76 (1H, dd, J9a/8=3.6, J9a/9b=12.0)
3.95 (1H, ddd, J8/9a=4.7, J8/7=10.2, J8/9b=12.4) 1.41 (1H, dd, J9a/8=4.7, J9a/9b=12.1)
3.99 (1H, ddd, J8/9b=4.4, J8/7=11.5, J8/9a=11.6) 1.90 (1H, dd, J9a/8=11.6, J9a/9b=11.9)
4.12 (1H, ddd, J8/9a=4.6, J8/7=10.0, J8/9a=11.1) 1.70 (1H, dd, J9a/8=4.6, J9a/9b=12.5)
1.34 (1H, dd, J9b/9a=12.1, J9b/8=12.4) 6.40 (1H, s)
1.83 (1H, dd, J9b/8=4.4, J9b/9a=11.9)
1.56 (1H, dd, J9b/8=11.6, J9b/9a=12.0) 6.13 (1H, d, J13a/7=3.1)
6.16 (1H, d, J13a/7=3.0)
1.60 (1H, dd, J9b/8=11.1, J9b/9a=12.5) 6.37 (1H, s)
5.95 (1H, d, J13b/7=2.8)
5.80 (1H, s)
5.98 (1H, d, J13b/7=2.6)
5.76 (1H, s)
0.91 (3H, s)
0.88 (3H, s)
1.12 (3H, s)
1.08 (3H, s)
5.10 (1H, s)
5.04 (1H, s)
3.22 (1H, dd, J15a/3a=1.8, J15a/15b=3.2)
3.20 (1H, dd, J15a/3a=1.5, J15a/15b=3.4)
15b 16 3’ 4’ 5’ 3’’
4.78 (1H, s) 5.24 (1H, q, J3’/5’=6.3) 1.40 (3H, s) 1.34 (3H, d, J5’/3’=6.3) 6.14 (1H, qq) J3’’/5’’=1.3, J3’’/4’’=7.3 1.93 (3H, dq, J4’’/5’’=1.5, J4’’/3’’=7.3) 1.79 (3H, dq, J5’’/3’’=1.3, J5’’/4’’=1.5) 3.23 (1H, s)
4.76 (1H, s) 3.75 (3H, s) 5.22 (1H, q, J3’/5’=6.2) 1.42 (3H, s) 1.36 (3H, d, J5’/3’=6.2) 6.11 (1H, q, J3’’/4’’=7.3)
2.90 (1H, d, J15b/15a=3.2) 3.12 (1H, q, J3’/4’=5.4) 1.35 (3H, d, J4’/3’=5.4) 1.66 (3H, s) -
2.78 (1H, d, J15b/15a=3.4) 3.74 (3H, s) 3.07 (1H, q, J3’/4’=5.3) 1.32 (3H, d, J4’/3’=5.3) 1.64 (3H, s) -
1.93 (3H, d, J4’’/3’’=7.3)
1.79 (3H, s)
3.30 (1H, s)
4.00 (1H, s)
Position 1 2a
4’’ 5’’ OH
Eudesmanolides from Dimerostemma arnottii
Natural Product Communications Vol. 5 (5) 2010 671
Table 2: 2D NMR spectroscopic data for compounds 1 to 4 (400 MHz, CDCl3). Position C H 1 1 2
1 H2a; H2b
2 H2a; H2b H1; H3b H1; H3b H2a; H3b H2a; H3a -
COSY 3 H2a; H2b
2 H3a; H14
H1; H2b; H3a; H3b H1; H2b; H3a; H3b H2a; H2b; H3b H2a; H2b; H3a -
H1; H2b; H3a; H3b H1; H2a; H3a; H3b H2a; H2b; H3b; H15a H2a; H2b; H3a -
4 H1*; H3b; H9b; H14 H3a; H3b
H15a; H15b -
H1; H15a; H15b -
H1; H2b -
H3a; H5; H6
H1; H9a; H14; H15a; H15b H5 H9a; H13a; H13b
H1; H9a; H9b; H14
H1; H2b; H3a; H3b H1; H2a; H3a; H3b H2a; H2b; H3b H2a; H2b; H3a -
H14; H15a; H15b
H5; H7 H6; H8; H13a; H13b
H5; H7 H6; H8
H5; H7 H6; H8; H13a; H13b
H5; H7 H6; H8
9a 9b -
H6; H7; H9a; H9b H8; H9b H8; H9a -
H7; H9a; H9b H8; H9b H8; H9a -
H7; H9a; H9b H8; H9b H8; H9a -
H7; H9a; H9b H8; H9b H8; H9a -
H14 H5; H14
13a 13b 14
H7 H7 -
H7 H7 -
H7; H13a; H13b; H16 H9b; H14*
15a 15b 16 3’ 4’ 5’ 3’’ 4’’ 5’’
H5’ H3’ H4’’ H3’’ -
H3a; H15b H15a H4’ H3’ -
H5’ H3’ H4’’; H5’’ H3’’; H5’’ H3’’; H4’’
H3a; H15b H15a H4’ H3’ -
H5; H9a; H9b H3a; H5 -
H1; H4’; OH H4’; H5’ H4’; H5’ H4’* H4’; H5 H4’’; H5’’ H3’’; H5’’ H3’’; H4’’
H1; H4’ H4’; H5’ H4’; H5’ H4’* H3’; H5’* H5’’ H4’’; H5’’ H4’’; H5’’ H4’’* H5’’*
H1; H2a; H5’ H4’; H5’ H4’; H5’ H3’ H3’ -
14 15 16 1’ 2’ 3’ 4’ 5’ 1’’ 2’’ 3’’ 4’’ 5’’
HMBC 3 H14
4 H2a; H2b
H3a; H2b; H2b;
H7; H9a; H9b H14 H5; H9a; H9b; H14
H5; H7; OH H6; H9a; H9b; H13a; H13b; OH H7; H9a; H9b; OH H14 H2b; H5; H9a; H9b; H14 H6; H7; H13a H13a; H13b
H1; H2 H3a; H3b; H5 H1; H3b; H5*; H9a; H14; OH H5; OH H6; H7*; H9a; H13a; H13b; OH H7; H9a; H9b; H14 H14 H5; H9a; H9b; H14 H6; H7; H13a; H13b H7; H13a; H13b; H16 H7; H13a* H5; H9a; H9b; H14* H5 H16* H1; H5’ H4’; H5’ H4’; H5’ H3’; H4’* H5’* -
* 1J observed in HMBC experiments.
important for the elucidation of the structure of 1. With the exception of the epoxide ring along C4-C15 and the epoxyangelate at C1, the structure of 1 is identical to that of 3 (Figure 1). After careful analysis of the NMR spectroscopic data, the positions from 1-15 of 1 could be fully assigned. The 1H NMR signals of H3’’, H4’’, and H5’’ of the side chain ester at C1 led us to consider the presence of either the angelate or tiglate moiety. However, the typical quartet of the olefinic hydrogen at δ 6.14 (H3’’), together with 13C NMR data, confirmed the presence of the angelate moiety. Nevertheless, additional signals (H2’ to H5’) that did not correlate with any atom of the eudesmane skeleton suggested an ester of higher complexity at C1. Thus, HMBC and previously published data [12,13] were used for the assignment of all the positions of this ester, as shown in
Tables 1, 2, and 3. The HR-ESI-MS data helped us to confirm the structure of 1 as shown in Figure 1. The structural elucidation of compound 2 was based on the analysis of the NMR spectra of 1. The only difference between the structures of 1 and 2 is the same as that observed for 3 and 4; i.e., the presence of a lactone function instead of a methyl ester at C12, respectively. The HR-ESI-MS data of 2 confirmed its structure as shown in Figure 1. For all compounds, the 13C NMR signals were assigned with the aid of HMQC information, followed by the use of HMBC data for assignment of the quaternary carbon atoms. Special highlights of the 2D assignments are the observed correlations between C1’ and H1 for all the structures in HMBC. This procedure confirmed the
672 Natural Product Communications Vol. 5 (5) 2010 Table 3: 13C NMR spectroscopic data for compounds 1 to 4 (100 MHz, CDCl3). Position 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1’ 2’ 3’ 4’ 5’ 1’’ 2’’ 3’’ 4’’ 5’’
1 78.2 28.1 32.2 144.4 53.1 74.0 53.6 76.6 37.5 42.1 137.6 170.3 120.5 19.9 109.3 175.2 67.6 75.8 22.9 13.6 166.8 127.3 141.4 16.3 20.6
2 79.1 28.1 32.3 145.0 51.0 68.0 59.7 67.1 42.6 40.1 138.6 167.6 129.1 18.6 109.4 52.1 174.7 76.4 75.0 22.3 13.6 167.8 127.7 140.7 16.2 20.7
δC in ppm 3 76.3 25.4 30.0 61.1 47.7 68.1 54.6 75.5 38.6 42.8 136.9 170.1 121.1 20.4 51.9 169.2 60.1 60.0 14.1 19.6 -
4 76.4 25.4 30.1 61.1 45.5 67.6 59.1 66.4 42.8 40.6 137.3 167.2 129.4 19.3 51.3 51.8 169.0 59.7 59.9 13.8 19.4 -
position of ester moieties in the four structures. HMQC data are not presented in Table 2 because all possible correlations were clearly observed for 1-4. The relative stereochemistry of positions 1, 6, 7, 8, and 10 for all the compounds was fully confirmed by NOEDIFF experiments. An intense NOE effect was observed between H6, H8, and H14 with irradiation at any of these positions. On the other hand, irradiation of H5 and H7 caused no effect on the signals of H6, H8, and H14. It should be pointed out that eudesmanes with a methyl ester at C12, as displayed by the structures of compounds 2 and 4 as well as the complex side chain ester of 1 and 2, are very rare in Asteraceae. A few similar eudesmane methyl esters were found in taxa of the tribe Cardueae , while the only report in subtribe Verbesininae so far was in Geraea viscida (A. Gray) S.F.Blake . Although we believe that compounds 2 and 4 are natural, the hypothesis that they may actually be artifacts formed during the isolation process cannot be discarded. Several sesquiterpene lactones of the eudesmanolide, guaianolide, germacrolide, melampolide, and other minor subgroups have been described in the subtribe Verbesininae. The terpenoids isolated from D. arnottii (formerly A. arnottii) show very close similarity to the
Ambrosio et al.
eudesmanolides previously reported in other Dimerostemma species, not only with regard to their skeletal subtypes but also with respect to the unique substitution pattern; for example, α-oriented ester and hydroxyl group at C1 and C8, respectively, and exocyclic double bond or epoxide ring along C4-C15 (dimerostemmolides) [2-5,11]. Thus, based on the substitution pattern of the eudesmane framework of the four compounds, the new combined species investigated herein presents the same chemical pattern as the other previously investigated Dimerostemma species. Therefore, our chemical data are supported by phylogenetic studies using molecular data and both corroborate the transfer of the genus Angelphytum into Dimerostemma. Experimental General experimental procedures: IR spectra were recorded in CHCl3 using a Nicolet-Protégé 460 spectrometer. NMR spectra were acquired on a Bruker DPX 400 spectrometer (400 MHz for 1H and 100 MHz for 13C). Samples were dissolved in CDCl3, and the spectra were calibrated from the solvent signals observed at δ 7.26 (1H) or 77.0 (13C). High resolution ESI-MS spectra were obtained using an UltrO-TOF (Bruker Daltonics) fitted with an electrospray ion source operating in the positive ion mode. Vacuum liquid chromatography (VLC)  was carried out using silica gel 60H (Merck, art. 7736) in glass columns with 5-10 cm i.d. Flash chromatography  was performed with silica gel 60 (Merck, art. 9385) in a 450-25 mm glass column, using a flow rate of 5 mL/min. High performance liquid chromatography (HPLC) analyses were accomplished on a Shimadzu SLC-10Avp liquid chromatography controller operating with the Class-VP software v. 5.02 and equipped with a Shimadzu UV-DAD detector SPD-M10Avp and a Shimadzu ODS column (4.6 x 250 mm, 5 µm, 100 Å). Plant material: Leaves from D. arnottii were collected and identified by Mara A. G. Magenta in March 2003 in Bonito, MS, Brazil (20o44’42’’S, 56o51’58’’W, 626 m). A voucher specimen (MM #552) is deposited at the SPF Herbarium, Universidade de São Paulo, São Paulo, SP, Brazil. Extraction and isolation: Air-dried powdered leaves of D. arnottii (150.0 g) were macerated with CH2Cl2 at room temperature (ca. 25°C), yielding 3.7 g of crude extract. This material was dissolved in MeOH and diluted with H2O (7:3 v/v) to give 2.4 g of an organicsoluble residue (phase A) after wax precipitation and solvent evaporation. Phase A was chromatographed over silica gel using VLC with increasing amounts of EtOAc in n-hexane as eluent. This procedure furnished
Eudesmanolides from Dimerostemma arnottii
6 fractions (300 mL each), namely F1 (190.0 mg), F2 (183.0 mg), F3 (276.0 mg), F4 (535.0 mg), F5 (830.0 mg), and F6 (97.0 mg). IR spectral analysis of fractions F4 and F5 revealed strong bands at ca. 1760 cm-1 due to the carbonyl stretching of γ-lactones, thus indicating the presence of sesquiterpene lactones. F4 was then fractionated by flash chromatography (isocratic, n-hexane/EtOAc/CHCl3 2:1:2), yielding 8 sub-fractions after TLC analysis. Approximately 20.0 mg of the sub-fraction F4.6 (96.6 mg) was further purified by reversed phase HPLC using an analytical column. After repeated injections (50 μL; MeCN/H2O, 55:45; flow rate 1.0 mL/min.; UV detection at 210 nm) of samples containing 0.5 mg each, the two main compounds 1 (4.2 mg) and 2 (6.5 mg) were isolated. F5 was initially fractionated over silica gel by VLC, as described above, to give an additional 8 sub-fractions (F5.1 to F5.8). F5.3 (120.0 mg) and F5.5 (80.0 mg) were further fractionated using flash chromatography (n-hexane/EtOAc/CHCl3 2:5:3 + 1% HOAc). A white solid mass appeared in the sub-fraction F5.5.3 (12.0 mg), which was identified as compound 3. After TLC analysis, the sub-fraction F5.3.4 (15.0 mg) showed a main spot (4, 5.0 mg), which was later purified by reversed phase HPLC as previously described (50 μL; MeCN/H2O 1:1; flow rate 0.9 mL/min.; 210 nm).
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Compound 1 H NMR: Table 1. 13 C NMR: Table 3. HR-ESI-MS: m/z [M + Na]+ 485.2172 (calcd for C25H34O8Na+, 485.2146). 1
Compound 2 H NMR: Table 1. 13 C NMR: Table 3. HR-ESI-MS: m/z [M + Na]+ 517.2433 (calcd for C26H38O9Na+, 517.2408). 1
Compound 4 H NMR: Table 1. 13 C NMR: Table 3. HR-ESI-MS: m/z [M + Na]+ 433.1866 (calcd for C21H30O8Na+, 433.1833) 1
Acknowledgments - The authors are grateful to FAPESP for financial support and to CNPq and CAPES for funding and grants. Special thanks to Professor N.P. Lopes and Mr J.C. Tomaz for HR-ESI-MS experiments.
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Computer-aided Structure Elucidation of Neolignans Mara B. Costantin, Marcelo J. P. Ferreira, Gilberto V. Rodrigues and Vicente P. Emerenciano
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Natural Product Communications 2010 Volume 5, Number 5 Contents Original Paper
A new Bisabolane Derivative of Leontopodium andersonii Stefan Schwaiger, Stefanie Hehenberger, Ernst P. Ellmerer and Hermann Stuppner
Eudesmanolides and Methyl Ester Derivatives from Dimerostemma arnottii Sérgio Ricardo Ambrosio, Ricardo Stefani, Vladimir Constantino Gomes Heleno, Márcio Antônio de Menezes, Antonio Gilberto Ferreira, Paulo Gustavo Barboni Dantas Nascimento, Mara Angelina Galvão Magenta and Fernando Batista Da Costa
Acid Rearrangment of Epoxy-germacranolides and Absolute Configuration of 1β,10α-Epoxy-salonitenolide Sergio Rosselli, Antonella Maria Maggio, Rosa Angela Raccuglia, Susan L. Morris-Natschke, Kenneth F. Bastow, Kuo-Hsiung Lee and Maurizio Bruno
Sesquiterpenes Lactones and Flavonoids from Eremanthus argenteus (Asteraceae) Humberto Takeshi Sakamoto, Eugênio Paceli Laudares, Antônio Eduardo Miller Crotti, Norberto Peporine Lopes, Walter Vichnewski, João Luis Callegari Lopes and Vladimir Constantino Gomes Heleno
Constituents of Calamintha ashei: Effects on Florida Sandhill Species Marios A. Menelaou, Hidelisa P. Henandez, Francisco A. Macías, Jeffrey D. Weidenhamer, G. Bruce Williamson, Frank R. Fronczek, Helga D. Fischer and Nikolaus H. Fischer
Biotransformation of Sesquiterpenoids from Liverworts by Fungi and Mammals Yoshinori Asakawa, Toshihiro Hashimoto and Yoshiaki Noma
Identification and Functional Characterization of a new Sunflower Germacrene A Synthase (HaGAS3) Jens Göpfert, Anna-Katharina Bülow and Otmar Spring
Anticancer Activity of Andrographolide Semisynthetic Derivatives Vidya Menon and Sujata Bhat
Prenylated Pterocarpanes from Erythrina melanacantha Wera Hauschild, Patrick B. Chalo Mutiso and Claus M. Passreiter
Natural Products from Scorzonera aristata (Asteraceae) Manuela Jehle, Johanna Bano, Ernst P. Ellmerer and Christian Zidorn
Protective Effect on Human Lymphocytes of Some Flavonoids Isolated from Two Achillea Species Ivana Aljančić,, Miroslava Stanković, Vele Tešević, Ljubodrag Vujisić, Vlatka Vajs and Slobodan Milosavljević
Effects of Caffeoylquinic Acid Derivatives and C-Flavonoid from Lychnophora ericoides on in vitro Inflammatory Mediator Production Michel David dos Santos, Guanjie Chen, Maria Camila Almeida, Denis Melo Soares, Glória Emília Petto de Souza, Norberto Peporine Lopes and R. Clark Lantz
LC-MS-MS Identification and Determination of the Flavone-C-Glucoside Vicenin-2 in Rat Plasma Samples Following Intraperitoneal Administration of Lychnophora Extract Valquiria A. Polisel Jabor, Denis Melo Soares, Andrea Diniz, Glória Emilia Petto de Souza and Norberto Peporine Lopes
A New Bianthracene C-arabinopyranoside from Senna septemtrionalis Gizachew Alemayehu, Legesse Adane and Berhanu M. Abegaz
Continued inside backcover