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Scuteparvin, a new neoclerodane diterpenoid from Scutellaria parvula
Biochemical Systematics and Ecology 32 (2004) 755–759 www.elsevier.com/locate/biochemsyseco
Scuteparvin, a new neoclerodane diterpenoid from Scutellaria parvula Maurizio Bruno a,, Sergio Rosselli a, Antonella Maggio a, Franco Piozzi a, Leonardo Scaglioni b, Orietta Servettaz c a
Dipartimento di Chimica Organica ‘‘E. Paterno`’’, Universita` di Palermo, Viale delle Scienze, Parco d’Orleans II, 90128, Palermo, Italy b Dipartimento di Scienze Molecolari Agroalimentari, Universita` di Milano, via Celoria 2, 20133 Milano, Italy c Dipartimento di Biologia, Universita` di Milano, via Celoria 3, 20133 Milano, Italy Received 22 October 2003; accepted 9 January 2004
Abstract The diterpenoid fraction occurring in the acetone extract of the aerial parts of Scutellaria parvula has been investigated. Only one neoclerodane diterpenoid, scuteparvin, was isolated and its structure elucidated as 4a,18-epoxy-6a-trans-cinnamoyloxy-neoclerod-13-en-15, 16-olide, a new natural product. Scuteparvin is quite similar to the already known ajugarin V from Ajuga remota, the only difference being the occurrence of a trans-cinnamoyl ester system instead of an acetate on the 6a-OH group. This finding confirms that the genera Scutellaria and Ajuga are closely related taxonomically. # 2004 Elsevier Ltd. All rights reserved. Keywords: Scutellaria parvula; Lamiaceae; Diterpenes; Neoclerodane
1. Introduction The genus Scutellaria, Lamiaceae (Labiatae), occurs with ca. 360 species spread throughout the world (Willis, 1966). It is rich with neoclerodane diterpenoids, that usually show some heterocyclic functions: epoxides, lactones, hydrofurans groups. Many of these products have a remarkable antifeedant activity against pest insects.
Corresponding author. Tel.: +39-91-59–69-05; fax: +39-91-59-68-25. E-mail address: [email protected] (M. Bruno).
0305-1978/$ - see front matter # 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.bse.2004.01.002
756
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
The chemistry of the diterpenoids from Scutellaria was recently reviewed (Bruno et al., 2002). Continuing our research program on the components of this genus, we investigated Scutellaria parvula Michx., a species originating from North America (Florida, Texas to Quebec) and never studied previously.
2. Material and methods Scutellaria parvula Michx. was cultivated in the Orto Botanico ‘‘G. E. Ghirardi’’ of the University of Milan, at Toscolano (Garda Lake, Brescia), Italy, from seeds provided by the Jardin Botanique de Lausanne, Lausanne, Switzerland. Plant materials were collected in August 2000, and voucher specimens (No. 7694) have been deposited in the Herbarium, Dipartimento di Biologia, University of Milan, Italy. Optical rotation was measured on a Perkin-Elmer 141 polarimeter. IR spectrum was obtained on Perkin-Elmer 1310 spectrophotometer. 1H and 13C NMR spectra were obtained on Bruker AMX-600 operating at 600.13 and 150.9 MHz for proton and carbon, respectively. DEPT experiment was acquired on a Bruker AMX-300 spectrometer. Measurements were made in CDCl3 solution, chemical shifts were referenced to TMS set at 0 ppm, and coupling constants are given in Hz. Heteronuclear two-dimensional 1H-13C correlations, one-bond HMQC (heteronuclear multiple quantum correlation) (Bax and Morris, 1981) and long-range HMBC (heteronuclear multiple bond correlation) (Bax and Summers, 1986), were carried out in the 1H-detected mode with broad-band decoupling in the 13C domain. ESIMS was recorded on an Applied Biosystems API 2000 instrument. Elemental analysis was made with a Perkin Elmer 240 apparatus. UV spectrum was obtained on a Jasco 7800 UV-Vis spectrophotometer. Merck Si gel no. 7734 (70–230 mesh) deactivated with 15% H2O, w/v, was used for column chromatography. Dried and finely powdered aerial parts of S. parvula (450 g) were extracted 3 times with Me2CO (each 10 L) at room temperature for 1 week. After filtration, v the solvent was evaporated at low temperature (35 C) and reduced pressure yielding a gum (18 g) which was adsorbed on 40 g of silica gel (Merck No. 7734, deactivated with 15% H2O) and was subjected to CC over 400 g of the same adsorbent, 50 ml fractions being collected as follows: 1-25 (petrol); 27-33 (petrol-EtOAc, 9:1); 34-56 (petrol-EtOAc, 4:1); 57-63 (petrol-EtOAc, 1:1); 64-73 (petrol-EtOAc, 3:7); 74-99 (EtOAc), 100-106 (EtOAcMeOH, 9:1) Fractions 64–71 (1.2 g) were rechromatographed over silica gel with petrol and a gradient of petrol/EtOAc to give several subfractions. The subfractions eluted with petrol-EtOAc 3:2 were subjected to CC using CH2Cl2 and CH2Cl2–MeOH 98:2 as eluent to give 30 mg of compound 2. Compound 2: Amorphous solid; [a]25DV – 6.7 (c ¼ 0:45, CHCl3); UV kmax (EtOH) nm (e): 217 (10918), 278 (22190); IR mmax (film): 2933, 2871, 1778, 1747,
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
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Table 1 1 H NMR, 13C NMR and HMBC of scuteparvin (2) in CDCl3 H
ppm
J
Hz
C
ppm
HMBC
1a 1b 2a 2b 3a 3b 6b 7a 7b 8b 10b 11a 11b 12a 12b 14 (2H)16 Me17 18a 18b Me19 Me20 20 30 200 300 400 500 600
1.48 o.s. 1.53 o.s. 1.86 ddddd 1.28 ddddd 2.08 dddd 0.89 ddd 4.76 dd 1.58 o.s. 1.50 o.s. 1.60 o.s. 1.24 dd 1.58 o.s. 1.50 o.s. 2.23 dddd 2.09 dddd 5.79 dddd 4.69 d 0.78 d 3.14 dd 2.31 d 1.30 s 0.78 s 6.34 d 7.57 d 7.44 m 7.29 m 7.29 m 7.29 m 7.44 m
1a,1b 1a,2a 1a,2b 1a,10b 1b,2a 1b,2b 1b,10b 2a,2b 2a,3a 2a,3b 2b,3a 2b,3b 3a,3b 3a,18 6b,7a 6b,7b 7a,7b 7a,8b 7b,8b 8b,17 11a,11b 11a,12a 11a,12b 11b,12a 11b,12b 12a,12b 12a,14 12b,14 14,16 18a,18b 20 ,30
n.d. 4.5 13.2 12.0 2.6 4.2 3.2 13.2 4.5 2.6 13.2 4.2 13.2 2.4 10.8 4.7 n.d. n.d. n.d. 6.4 n.d. 13.0 4.8 4.2 12.8 16.1 1.5 1.5 1.5 4.2 16.0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 10 20 30 100 200 e 600 300 e 500 400
20.64 t 24.97 t 32.00 t 66.66 s 42.03 s 73.75 d 32.86 t 34.65 d 38.68 s 47.46 d 35.03 t 21.96 t 170.15 s 115.32 d 173.79 s 73.01 t 15.39 q 52.07 t 14.48 q 17.58 q 166.22 s 118.76 d 144.46 d 134.58 s 128.10 d 128.74 d 130.05 d
H-10 H-10, H-3a, H-3b H-18b H-6, H-3a,H-2a, Me-19, H-3b H-6 H-7a, Me-19 H-6 Me-17 H-10, Me-17 H-2a, Me-19, Me-20 H-14 H-14, H-16, H-12a, H-12b, H-11a, H-11b H-16, H-12a, H-12b H-14, H-16 H-14 H-3a, H-3b H-6 H-10 H-30 , H-20 , H-6 H-30 H-30 , H-20
o.s. = overlapped signal. n.d. = not determined.
1701 1637 1448, 1310, 1280, 1184, 1124, 1062, 1009, 966, 887, 767 cm1; 1H NMR (CDCl3): see Table 1; 13C NMR: see Table 1; MS m/z (rel. int.): 487 (100) [M+Na]+, 464 (60) [M]+, 317 (15) [M-C9H7O2]+, 214 (21). Anal. Calcd for C29H36O5: C, 74.97; H, 7.81. Found: C, 74.82; H, 7.90.
3. Results and discussion From aerial parts of S. parvula, we isolated a not previously described neoclerodane diterpenoid, scuteparvin. Its MS and elemental analysis were indicative of a C29H36O5 formula. The UV spectrum suggested the presence of an a,b unsaturated-c-lactone [kmax (EtOH) 217 nm] that was confirmed by the signals, in the
758
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
1
H NMR spectrum (Table 1) , at d 5.79 (1H dddd J ¼ 1:5, 1.5, 1.5, 1.5 Hz) and at d 4.69 (2H, d, J ¼ 1:5 Hz). Furthermore, the 1H NMR spectrum showed signals of two tertiary methyl groups (d 0.78, 3H, s and d 1.30, 3H, s), a secondary methyl group (d 0.78, 3H, d, J ¼ 6:4 Hz), two protons of a methylene epoxide (d 3.14, 1H, dd, J ¼ 4:2, 2.4 Hz and d 2.31, 1H, d, J ¼ 4:2 Hz) and a proton (d 4.76, 1H, dd, J ¼ 10:8, 4.7 Hz) geminal to an esterified secondary hydroxy group; moreover, signals for a transcinnamoyl system were present. These data were similar to those of ajugarin V (1), isolated from Ajuga remota (Kubo et al., 1983), apart the aromatic system missing in 1. The 13C NMR spectrum (Table 1) confirmed the attribution of the above groups and the similarity with the 13C NMR spectrum of ajugarin V. On the basis of these data, structure 2 was assigned to scuteparvin.
Based on the results of heteronuclear two-dimensional 1H-13C correlations, onebond HMQC and long-range HMBC we were able to assign unambiguously all the carbons and to identify all the protons. It has to be pointed out that some of the carbon attributions of ajugarin V, reported in literature (Kubo et al., 1983), have to be amended. In fact, the signals at dC 24.97 shows connectivity with H-3a (dH 2.08) and H-10 (dH 1.24) and consequently it must be assigned to carbon 2; similarly the correlation between signal at dC 32.00 and H-18b (dH 2.31) indicates this carbon as C-3. Carbon 12 (dC 21.96) was clearly identified by its correlation with H-14 (dH 5.79) and by the connectivities of its protons with carbon 13 (dC 170.15) and carbon 14 (dC 115.32). Similarly the connectivities of H-11a (dH 1.58) and H11b (dH 1.50) with carbon 13 (dC 170.15) allowed us to assign carbon 11 at dC 35.03. Therefore, we believe that the signals at dC 23.3, 25.3, 32.4 and 35.5 and attributed to C-2, C-3, C11 and C-12 for compound 1 (Kubo et al., 1983), have to be reassigned to C-12, C-2, C-3 and C-11, respectively. Although the absolute stereochemistry was not ascertained, it may be suggested that scuteparvin belongs to the neoclerodane series of diterpenoids isolated from
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
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species of Scutellaria. This finding confirms that the genera Scutellaria and Ajuga are rather related chemotaxonomically, even not so related morphologically. In fact, the genera Ajuga and Teucrium belong to the tribe Ajugaeae, whereas the genus Scutellaria belongs to the tribe Scutellarieae. However, the neoclerodane diterpenoids synthesized by species of Ajuga and Scutellaria always show the oxigenated heterocyclic system as furofuran or lactone rings, whereas the furan system is never present. On the contrary the furan ring is typical of the neoclerodane diterpenoids occurring in the species of the genus Teucrium. Acknowledgements This work was supported by grants (PRIN 2003) of the Italian Ministry of University and Research (M.I.U.R.). References Bax, A., Morris, G., 1981. An improved method for heteronuclear chemical shift correlation by twodimensional NMR. J. Magn. Reson. 42, 501–505. Bax, A., Summers, M.F., 1986. 1H and 13C assignments from sensitivity-enhanced detection of heteronuclear multlipe-bond connectivity by 2D multiple quantum NMR. J. Am. Chem. Soc. 108, 2093–2094. Bruno, M., Piozzi, F., Rosselli, S., 2002. Natural and hemisynthetic neoclerodane diterpenoids from Scutellaria and their antifeedant activity. Nat. Prod. Rep. 19, 357–378. Kubo I., Fukuyama Y., Chapya A., 1983. Structure of Ajugarin V. Chem. Letters, 223-224. Willis, J.C., 1966. A Dictionary of the Flowering Plants and Ferns, 7th ed. Cambridge University Press, UK.
Scuteparvin, a new neoclerodane diterpenoid from Scutellaria parvula Maurizio Bruno a,, Sergio Rosselli a, Antonella Maggio a, Franco Piozzi a, Leonardo Scaglioni b, Orietta Servettaz c a
Dipartimento di Chimica Organica ‘‘E. Paterno`’’, Universita` di Palermo, Viale delle Scienze, Parco d’Orleans II, 90128, Palermo, Italy b Dipartimento di Scienze Molecolari Agroalimentari, Universita` di Milano, via Celoria 2, 20133 Milano, Italy c Dipartimento di Biologia, Universita` di Milano, via Celoria 3, 20133 Milano, Italy Received 22 October 2003; accepted 9 January 2004
Abstract The diterpenoid fraction occurring in the acetone extract of the aerial parts of Scutellaria parvula has been investigated. Only one neoclerodane diterpenoid, scuteparvin, was isolated and its structure elucidated as 4a,18-epoxy-6a-trans-cinnamoyloxy-neoclerod-13-en-15, 16-olide, a new natural product. Scuteparvin is quite similar to the already known ajugarin V from Ajuga remota, the only difference being the occurrence of a trans-cinnamoyl ester system instead of an acetate on the 6a-OH group. This finding confirms that the genera Scutellaria and Ajuga are closely related taxonomically. # 2004 Elsevier Ltd. All rights reserved. Keywords: Scutellaria parvula; Lamiaceae; Diterpenes; Neoclerodane
1. Introduction The genus Scutellaria, Lamiaceae (Labiatae), occurs with ca. 360 species spread throughout the world (Willis, 1966). It is rich with neoclerodane diterpenoids, that usually show some heterocyclic functions: epoxides, lactones, hydrofurans groups. Many of these products have a remarkable antifeedant activity against pest insects.
Corresponding author. Tel.: +39-91-59–69-05; fax: +39-91-59-68-25. E-mail address: [email protected] (M. Bruno).
0305-1978/$ - see front matter # 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.bse.2004.01.002
756
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
The chemistry of the diterpenoids from Scutellaria was recently reviewed (Bruno et al., 2002). Continuing our research program on the components of this genus, we investigated Scutellaria parvula Michx., a species originating from North America (Florida, Texas to Quebec) and never studied previously.
2. Material and methods Scutellaria parvula Michx. was cultivated in the Orto Botanico ‘‘G. E. Ghirardi’’ of the University of Milan, at Toscolano (Garda Lake, Brescia), Italy, from seeds provided by the Jardin Botanique de Lausanne, Lausanne, Switzerland. Plant materials were collected in August 2000, and voucher specimens (No. 7694) have been deposited in the Herbarium, Dipartimento di Biologia, University of Milan, Italy. Optical rotation was measured on a Perkin-Elmer 141 polarimeter. IR spectrum was obtained on Perkin-Elmer 1310 spectrophotometer. 1H and 13C NMR spectra were obtained on Bruker AMX-600 operating at 600.13 and 150.9 MHz for proton and carbon, respectively. DEPT experiment was acquired on a Bruker AMX-300 spectrometer. Measurements were made in CDCl3 solution, chemical shifts were referenced to TMS set at 0 ppm, and coupling constants are given in Hz. Heteronuclear two-dimensional 1H-13C correlations, one-bond HMQC (heteronuclear multiple quantum correlation) (Bax and Morris, 1981) and long-range HMBC (heteronuclear multiple bond correlation) (Bax and Summers, 1986), were carried out in the 1H-detected mode with broad-band decoupling in the 13C domain. ESIMS was recorded on an Applied Biosystems API 2000 instrument. Elemental analysis was made with a Perkin Elmer 240 apparatus. UV spectrum was obtained on a Jasco 7800 UV-Vis spectrophotometer. Merck Si gel no. 7734 (70–230 mesh) deactivated with 15% H2O, w/v, was used for column chromatography. Dried and finely powdered aerial parts of S. parvula (450 g) were extracted 3 times with Me2CO (each 10 L) at room temperature for 1 week. After filtration, v the solvent was evaporated at low temperature (35 C) and reduced pressure yielding a gum (18 g) which was adsorbed on 40 g of silica gel (Merck No. 7734, deactivated with 15% H2O) and was subjected to CC over 400 g of the same adsorbent, 50 ml fractions being collected as follows: 1-25 (petrol); 27-33 (petrol-EtOAc, 9:1); 34-56 (petrol-EtOAc, 4:1); 57-63 (petrol-EtOAc, 1:1); 64-73 (petrol-EtOAc, 3:7); 74-99 (EtOAc), 100-106 (EtOAcMeOH, 9:1) Fractions 64–71 (1.2 g) were rechromatographed over silica gel with petrol and a gradient of petrol/EtOAc to give several subfractions. The subfractions eluted with petrol-EtOAc 3:2 were subjected to CC using CH2Cl2 and CH2Cl2–MeOH 98:2 as eluent to give 30 mg of compound 2. Compound 2: Amorphous solid; [a]25DV – 6.7 (c ¼ 0:45, CHCl3); UV kmax (EtOH) nm (e): 217 (10918), 278 (22190); IR mmax (film): 2933, 2871, 1778, 1747,
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
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Table 1 1 H NMR, 13C NMR and HMBC of scuteparvin (2) in CDCl3 H
ppm
J
Hz
C
ppm
HMBC
1a 1b 2a 2b 3a 3b 6b 7a 7b 8b 10b 11a 11b 12a 12b 14 (2H)16 Me17 18a 18b Me19 Me20 20 30 200 300 400 500 600
1.48 o.s. 1.53 o.s. 1.86 ddddd 1.28 ddddd 2.08 dddd 0.89 ddd 4.76 dd 1.58 o.s. 1.50 o.s. 1.60 o.s. 1.24 dd 1.58 o.s. 1.50 o.s. 2.23 dddd 2.09 dddd 5.79 dddd 4.69 d 0.78 d 3.14 dd 2.31 d 1.30 s 0.78 s 6.34 d 7.57 d 7.44 m 7.29 m 7.29 m 7.29 m 7.44 m
1a,1b 1a,2a 1a,2b 1a,10b 1b,2a 1b,2b 1b,10b 2a,2b 2a,3a 2a,3b 2b,3a 2b,3b 3a,3b 3a,18 6b,7a 6b,7b 7a,7b 7a,8b 7b,8b 8b,17 11a,11b 11a,12a 11a,12b 11b,12a 11b,12b 12a,12b 12a,14 12b,14 14,16 18a,18b 20 ,30
n.d. 4.5 13.2 12.0 2.6 4.2 3.2 13.2 4.5 2.6 13.2 4.2 13.2 2.4 10.8 4.7 n.d. n.d. n.d. 6.4 n.d. 13.0 4.8 4.2 12.8 16.1 1.5 1.5 1.5 4.2 16.0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 10 20 30 100 200 e 600 300 e 500 400
20.64 t 24.97 t 32.00 t 66.66 s 42.03 s 73.75 d 32.86 t 34.65 d 38.68 s 47.46 d 35.03 t 21.96 t 170.15 s 115.32 d 173.79 s 73.01 t 15.39 q 52.07 t 14.48 q 17.58 q 166.22 s 118.76 d 144.46 d 134.58 s 128.10 d 128.74 d 130.05 d
H-10 H-10, H-3a, H-3b H-18b H-6, H-3a,H-2a, Me-19, H-3b H-6 H-7a, Me-19 H-6 Me-17 H-10, Me-17 H-2a, Me-19, Me-20 H-14 H-14, H-16, H-12a, H-12b, H-11a, H-11b H-16, H-12a, H-12b H-14, H-16 H-14 H-3a, H-3b H-6 H-10 H-30 , H-20 , H-6 H-30 H-30 , H-20
o.s. = overlapped signal. n.d. = not determined.
1701 1637 1448, 1310, 1280, 1184, 1124, 1062, 1009, 966, 887, 767 cm1; 1H NMR (CDCl3): see Table 1; 13C NMR: see Table 1; MS m/z (rel. int.): 487 (100) [M+Na]+, 464 (60) [M]+, 317 (15) [M-C9H7O2]+, 214 (21). Anal. Calcd for C29H36O5: C, 74.97; H, 7.81. Found: C, 74.82; H, 7.90.
3. Results and discussion From aerial parts of S. parvula, we isolated a not previously described neoclerodane diterpenoid, scuteparvin. Its MS and elemental analysis were indicative of a C29H36O5 formula. The UV spectrum suggested the presence of an a,b unsaturated-c-lactone [kmax (EtOH) 217 nm] that was confirmed by the signals, in the
758
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
1
H NMR spectrum (Table 1) , at d 5.79 (1H dddd J ¼ 1:5, 1.5, 1.5, 1.5 Hz) and at d 4.69 (2H, d, J ¼ 1:5 Hz). Furthermore, the 1H NMR spectrum showed signals of two tertiary methyl groups (d 0.78, 3H, s and d 1.30, 3H, s), a secondary methyl group (d 0.78, 3H, d, J ¼ 6:4 Hz), two protons of a methylene epoxide (d 3.14, 1H, dd, J ¼ 4:2, 2.4 Hz and d 2.31, 1H, d, J ¼ 4:2 Hz) and a proton (d 4.76, 1H, dd, J ¼ 10:8, 4.7 Hz) geminal to an esterified secondary hydroxy group; moreover, signals for a transcinnamoyl system were present. These data were similar to those of ajugarin V (1), isolated from Ajuga remota (Kubo et al., 1983), apart the aromatic system missing in 1. The 13C NMR spectrum (Table 1) confirmed the attribution of the above groups and the similarity with the 13C NMR spectrum of ajugarin V. On the basis of these data, structure 2 was assigned to scuteparvin.
Based on the results of heteronuclear two-dimensional 1H-13C correlations, onebond HMQC and long-range HMBC we were able to assign unambiguously all the carbons and to identify all the protons. It has to be pointed out that some of the carbon attributions of ajugarin V, reported in literature (Kubo et al., 1983), have to be amended. In fact, the signals at dC 24.97 shows connectivity with H-3a (dH 2.08) and H-10 (dH 1.24) and consequently it must be assigned to carbon 2; similarly the correlation between signal at dC 32.00 and H-18b (dH 2.31) indicates this carbon as C-3. Carbon 12 (dC 21.96) was clearly identified by its correlation with H-14 (dH 5.79) and by the connectivities of its protons with carbon 13 (dC 170.15) and carbon 14 (dC 115.32). Similarly the connectivities of H-11a (dH 1.58) and H11b (dH 1.50) with carbon 13 (dC 170.15) allowed us to assign carbon 11 at dC 35.03. Therefore, we believe that the signals at dC 23.3, 25.3, 32.4 and 35.5 and attributed to C-2, C-3, C11 and C-12 for compound 1 (Kubo et al., 1983), have to be reassigned to C-12, C-2, C-3 and C-11, respectively. Although the absolute stereochemistry was not ascertained, it may be suggested that scuteparvin belongs to the neoclerodane series of diterpenoids isolated from
M. Bruno et al. / Biochemical Systematics and Ecology 32 (2004) 755–759
759
species of Scutellaria. This finding confirms that the genera Scutellaria and Ajuga are rather related chemotaxonomically, even not so related morphologically. In fact, the genera Ajuga and Teucrium belong to the tribe Ajugaeae, whereas the genus Scutellaria belongs to the tribe Scutellarieae. However, the neoclerodane diterpenoids synthesized by species of Ajuga and Scutellaria always show the oxigenated heterocyclic system as furofuran or lactone rings, whereas the furan system is never present. On the contrary the furan ring is typical of the neoclerodane diterpenoids occurring in the species of the genus Teucrium. Acknowledgements This work was supported by grants (PRIN 2003) of the Italian Ministry of University and Research (M.I.U.R.). References Bax, A., Morris, G., 1981. An improved method for heteronuclear chemical shift correlation by twodimensional NMR. J. Magn. Reson. 42, 501–505. Bax, A., Summers, M.F., 1986. 1H and 13C assignments from sensitivity-enhanced detection of heteronuclear multlipe-bond connectivity by 2D multiple quantum NMR. J. Am. Chem. Soc. 108, 2093–2094. Bruno, M., Piozzi, F., Rosselli, S., 2002. Natural and hemisynthetic neoclerodane diterpenoids from Scutellaria and their antifeedant activity. Nat. Prod. Rep. 19, 357–378. Kubo I., Fukuyama Y., Chapya A., 1983. Structure of Ajugarin V. Chem. Letters, 223-224. Willis, J.C., 1966. A Dictionary of the Flowering Plants and Ferns, 7th ed. Cambridge University Press, UK.