1242
J. Nat. Prod. 1998, 61, 1242-1247
Neoclerodane Diterpenoids from Teucrium massiliense Gianfranco Fontana,† Maria Pia Paternostro,† Giuseppe Savona,*,† Benjamı´n Rodrı´guez,*,‡ and Marı´a C. de la Torre‡ Dipartimento di Chimica Organica, Universita` di Palermo, Via Archirafi 20, I-90123 Palermo, Italy, and Instituto de Quı´mica Orga´ nica, Consejo Superior de Investigaciones Cientı´ficas (CSIC), Juan de la Cierva 3, E-28006 Madrid, Spain Received April 10, 1998
A reinvestigation of the diterpene metabolites of Teucrium massiliense L. allowed the isolation of four new neoclerodane derivatives, teumassilenins A-D, together with all the diterpenoids previously reported as constituents of this plant. The structures of the new compounds (1-4) were established by chemical and spectroscopic means. A plausible biogenetic relationship between several of these substances is briefly discussed, and some unpublished physical and spectroscopic data of the previously known diterpenoid teumassin (5) are now reported. A large number of neoclerodane diterpenoids1 have been isolated from natural sources in the past few years.2,3 These compounds have attracted interest owing to their biological activities, especially as insect antifeedants4-9 and as antifungal, antimicrobial, and moluscicidal agents.2,3 More recently, interest in neoclerodanes has increased due to their hepatotoxic10-12 and tumoricidal13,14 actions. The species belonging to the genus Teucrium (family Labiatae) are the most abundant natural source of neoclerodane diterpenoids.2-8,15 In a continuation of our studies on Teucrium plants,16,17 we have reinvestigated T. massiliense L., a species already studied by us some years ago.18,19 We report here the structural elucidation of four new neoclerodanes found in this plant, as well as some unpublished physical and spectroscopic data of an already known diterpenoid. Results and Discussion Repeated chromatography of an Me2CO extract of the aerial parts of T. massiliense (see Experimental Section) led to the isolation of the new neoclerodanes teumassilenins A-D (1-4) along with teumassin (5), teumassilin (6), 6,19-diacetylteumassilin (7), teumarin (8), deacetylajugarin II, montanin C, and teucjaponin A, which were previously found in this plant.18,19 Teumassin (5), which has been described19 as an amorphous solid, was isolated as a crystalline substance, and its melting point and 13C NMR data (not previously reported19) are included in the Experimental Section and Table 2, respectively. The structures of the new diterpenoids were established as follows. Teumassilenin A (1) had the molecular formula C20H30O5, and its IR spectrum showed hydroxyl (3370 cm-1, br), furan (3160, 3130, 1600, 1510, 875 cm-1), and aldehyde (2720, 1720 cm-1) absorptions. Treatment of 1 with Ac2Opyridine yielded a triacetyl derivative (9, C26H36O8) for which the IR spectrum was devoid of any hydroxyl absorption, thus establishing that teumassilenin A possessed three alcohol functions. The 1H and 13C NMR spectra of 1 (Tables 1 and 2, respectively) were very similar to those of teumassilin18 (6), showing almost identical signals for a β-substituted furan, a hydroxymethylene group at the C-19 * To whom correspondence should be addressed. (G.S.) Tel.: 39 91 6164511. Fax: 39 91 6162454. (B.R.) Tel.: 34 1 5622900. Fax: 34 1 5644853. E-mail:
[email protected]. † Dipartimento di Chimica Organica, Universita ` di Palermo. ‡ Instituto de Quı ´mica Orga´nica, CSIC, Madrid.
10.1021/np980137r CCC: $15.00
position, an equatorial hydoxyl group attached to the C-6R position, and another secondary alcohol at C-12. The observed differences between the 1H and 13C NMR spectra of these diterpenoids were consistent with the presence in 1 of a C-18β aldehyde [δH-18 9.98, δH-4R 3.35; δC 46.8 d (C4) and 208.2 d (C-18)] instead of the 4R,18-oxirane of 6 [C-18 protons at δ 2.40 d, Jgem ) 4 Hz, and 3.15 dd, J18B,3R ) 2.4 Hz; δC 67.7 s (C-4) and 48.1 t (C-18)].18 The configuration of the C-18 aldehyde of 1 must be β, as was revealed by the coupling values of the H-4R proton with both of the C-3 methylene protons (J3R,4R ) 2.6 Hz, J3β,4R ) 5.1 Hz), which precluded an axial-axial relationship between these protons. This conclusion was strongly supported by NOE experiments because irradiation at δ 9.98 (aldehyde proton) caused NOE enhancement, among others, in the signal of the H-10β (δ 2.03) axial proton.
© 1998 American Chemical Society and American Society of Pharmacognosy Published on Web 08/11/1998
Neoclerodane Diterpenoids from Teucrium massiliense 1H
Table 1.
Journal of Natural Products, 1998, Vol. 61, No. 10 1243
NMR Spectral Data of Compounds 1-3 and 14
proton(s)
1
H-1R H-1β H-2R H-2β H-3R H-3β H-4R H-4β H-6β H-7R H-7β H-8β H-10β HA-11 HB-11 H-12 H-14 H-15 H-16 Me-17 HA-18 HB-18 HA-19 HB-19 Me-20 OAc
2
1.28 (dddd) ∼1.75a ∼1.70a 1.48 (ddddd) ∼1.75a 1.88 (dddd) 3.35 (ddd)
3
14
∼2.15a
b b b b b b
∼1.90a
∼1.80a ∼1.65a ∼2.10a ∼1.45a ∼1.65a
3.98 (br dd) ∼1.50a ∼1.50a ∼1.58a 2.03 (dd) 1.54 (dd) 1.79 (dd) 4.62 (dd) 6.31 (dd) 7.30 (t) 7.31 (m) 0.72 (3H, d) 9.98 (d)
b 3.53 (dd) b b b b b b 4.77 (dd) 6.39 (dd) 7.37a 7.37a 0.74 (3H, d) 4.89 (s)
3.75 (br d) 4.17 (d) 0.57 (3H, s)
3.84 (d) 4.05 (d) 0.51 (3H, s)
∼1.90a 5.17 (quint) 2.50 (ddd) 1.30 (ddd)c
3.76 (dd) 1.29 (ddd) ∼1.65a ∼1.70a ∼1.80a 1.47 (dd) 1.94 (dd) 4.78 (dd) 6.38 (dd) 7.35 (t) 7.34 (m) 0.72 (3H, d) 3.42 (d) 3.81 (d) 4.58 (d) 4.66 (d) 0.49 (3H, s)
4.83 (ddd) ∼2.10a 1.50 (br dt) 1.84 (ddq) ∼1.95a 2.19 (dd) 2.44 (dd) 5.35 (br t) 6.35 (dd) 7.45 (t) 7.41 (m) 1.11 (3H, d) 2.25 (d)d 3.02 (dd)e 4.47 (dd) 5.27 (d) 2.06 (3H, s) 2.01 (3H, s) 1.96 (3H, s)
JH,H (Hz)
1
2
3
14
1R,1β 1R,2R 1R,2β 1R,10β 1β,2R 1β,2β 1β,10β 2R,2β 2R,3R 2R,3β 2β,3R 2β,3β 3R,3β 3R,18B 3R,4R 3R,4β 3β,4R 3β,4β 4R,18 4β,18R 6β,7R 6β,7β 7R,7β 7R,8β 7β,8β 8β,17 11A,11B 11A,12 11B,12 14,15 14,16 15,16 18A,18B 19A,19B 19A,6β
12.7 3.9 12.5 12.5 b 4.5 2.7 13.6 b 3.2 13.3 4.5 12.8
b b b b b b b b b b b b b
b b b b b b b b b b b b b 0
b 3.4
14.8 2.2
11.4 4.8 13.0 11.9 b 6.6 15.5 2.6 9.0 1.6 0.6 1.6 13.0 6.0 0
11.2 4.2 13.7 11.1 3.8 6.9 14.1 8.2 8.9 1.7 0.9 1.7 4.1 13.3 1.0
b 2.5 b 3.5 2.4
2.6 b 5.1 b 2.4 11.0 4.0 b b b 6.1 15.6 3.9 7.8 1.8 0.8 1.7
0 11.4 4.0 b b b 6.6 b 3.4 8.0 1.8 0.9 b
11.7
