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6ß-Hydroxyteuscordin and 2/3-,6/9-Dihydroxyteuscordin Two New Diterpenoids from Teucrium scordium L.

Georgi Y. Papanov* and Peter Y. Malakov University of Plovdiv, 4000 Plovdiv, Bulgaria Z. Naturforsch. 87b, 519-520 (1982); received September 1, 1981 Teucrium scordium L., Lamiaceae, Clerodane Type, Furanoid Diterpene

Two new furanoid diterpenes of clerodane type, 6 /9-hydroxyteuscordin (1) and 2/?,6/3-dihydroxyteuscordin (3) have been isolated from Teucrium scordium var. scordium, Lamiaceae. Their structures and stereochemistry have been determined on the basis of chemical reactions and spectroscopic evidence.

Recently, we have described the isolation, struc-tures and stereochemistry of teuscordinon [1] and 6-ketoteuscordin and 6a-hydroxyteuscordin [2] from Teucrium scordium L. In continuation of this work, we habe isolated two new diterpenoids, 6/5-hydroxy-teuscordin (1) and 2/?,6/^dihydroxyteuscordin (3). 6/S-Hydroxyteuscordin, C20H22O6, m.p. 229-231 °C, [a]2D8 - 74.68° (c 0.158, acetone). MS: m/e 358 (M+). I R (KBr, cm-i) : 3460 (OH), 1760 and 1740 (two y-lactones), 1660 (double bond), 3140, 1505, 1600 and 875 (furan ring). XH NMR (CD3COCD3, (3): 0.96 (3H, d, J 7 Hz, s. CH3), 2.60 (1H, d, J 8 Hz, H - l l ) , 3.80 and 4.35 (2H, AB q, J 12 Hz, H2-19), 3.90 (1H, m, J 3 Hz, H-6), 5.44 (1H, t, J 8 Hz, H-12), 6.65 (1H, dd, J 3 and 7 Hz, H-3), 6.45 ( IH, m, ß-furan proton), 7.50 and 7.60 (2H, m, a-furan pro-tones).

The presence of a hydroxyl group in I was disclosed by treating with trichloroacetylisocyanate. The resonance of the corresponding > NH proton in the *H NMR spectrum is at <5 10.22 as a singlet and the methine proton moved to the high field (d 5.20, 1H, m, J 3 Hz).

The 1 H- 1 H couplings of C - 6 H showed that the H-6 in 1 is equatorial whereas the orientation of OH group is axial. Oxidation of 1 with chromium trioxide gave only teuscordinon (2) [1], identical with an autentic sample by mixed m.p., TLC, I R and XH NMR spectral comparison.

2/?,6/?-Dihydroxyteuscordin (3), C2oH2207, m.p. 228-230 °C, [a]p - 123.0° (c 0.167, acetone). MS: m/e 374 (M+). IR (KBr, cm-i) : 3440 (broad), 1770 and 1750 (two y-lactones), 1660 (double bond), 3140, 1505 and 870 (furan ring). *H NMR (C5D5N, Ö): 0.95 (3H, d, J 7 Hz, s. CH3), 1.54 (1H, ddd, J 4 and

* Reprint requests to Dr. G. Papanov. 0340-5087/82/0400-0519/$ 01.00/0

14 Hz, la -H) , 1.79 (1H, ddd, J 4 and 10Hz,7/5-H), 3.82 (1H, dd, J 2.5 and 14.0 Hz, 10-H), 4.10 and 4.70 (2H, AB q, J 12 Hz, H2-19), 4.35 (1H, t, J 3 Hz, H-6), 4.63 (1H, dd, J 4 and 12 Hz, 2£-H), 5.43 (1H, t, J 8 Hz, H-12), 6.39 (1H, m, £-furan proton), 7.50 (2H, m, a-furan protones), 6.90 (1H, d, J 7 Hz, H-3).

Acetylation of 3 gave a diacetate (4), C24H2609, m.p. 185-187 °C. The spectroscopic properties of 4 reveled the presence of a diacetate (CDCI3, d): 1.92 (3H, s, COOMe) and 2.04 (3H, s, COOMe). The protones at C-2 and C-6 move to the low field and resonated at 5.25 (1H, dd, J 4 and 12 Hz) and 5.20 (1H, t, J 3 Hz), while the double doublet of 10-H appeared at 2.98. The IR spectrum of 4 contained an intensive band at 1720-1740 and 1240 cm - 1 for two ester groups.

The two hydroxyl groups in 3 were also proved with trichloroacetylisocyanate. The corresponding > N H singlets appeared at 6 10.02 and 10.10.

The 2/5,6/3-dihydroxyteuscordin (3) was oxidized with Jones reagent to the 2-keto-6/?-hydroxyteus-cordin (5), C20H20O7, m.p. 223-225 °C, m/e 372 (M+).

1 E i = OH; R2 = H 2 Ri = R2 = O

3 Ri = R3 = OH; R2 = R4 = H

4 Ri = R3 = OAc; R2 = R4 = H

5 Ri = R2 = O; R3 = OH; R4 = H

520 G. Y. Papanov-P. Y. Malakov • 6 ß-Hydroxyteuscordin and 2ß-, 6/?-Dihydroxyteuscordin

In the XH NMR spectrum of 5 the signal from the 2-proton vanished, while the doublet from the 3-proton appeared as a singlet at 6.70. Furthermore the iH-^H couplings of 10-H in 5 are different (J 4 and 14 Hz) from the values found for 3 (J 2.5 and 14 Hz). These facts showed unambiguously that one of the hydroxil group is at C-2, ß oriented. The coupling of H-2 and H-6 indicated ß - OH support-ed by deshilding of H-10 and C-20 deshilding of H-19 (Table 1). On the base of the W NMR data for the 6-proton (<5 4.35, 1H, t, J 3 Hz) the other hydroxil group is at C-6, ß oriented. These data correspond with the values reported on related molecules of known geometry [3-6].

Table I. XH NMR spectral data of compound (400 MHz), CDC13, TMS as internal standard) [7].

1 -Ha 1.54 ddd 10 -H/3 3.10 dd l'-Tdß 2.05 d br 11 -Ha 2.62 dd 2 -Ha 4.51 dddd ll'-H/J 2.41 dd 2'-Hß 12 -H 5.37 dd 3 -Ha 6.87 d 14 -H 6.41 dd 3'-Hß 15 -H 7.48 s br 6 -Ha 4.17 dd 16 -H 7.45 dd 7 -Ha 2.33 ddd 17 -H3 1.06 d T-Hß 1.83 ddd 19 -Ha 4.57 d 8 -Tlß 2.16 ddq lQ'-Hß

OH -2.97 d 3.42 d

and 2.87 d

J (Hz): 1,1' = 1,10 = 14; 1,2 = r,2 = 4; l',10 = 2; 2,3 = 6.5 2,0H = 6,7 = 6,7' = 15; 7,8 = 13 ; 7',8 = 4; 8,17 = 7; 11,11' = 14 11,12 = 8; 11',12 = 9.5.

Experimental

The melting points are uncorrected and have been determined with a Kofler microhostage apparatus. IR spectra were recorded on KBr pellets. *H NMR spectra were obtained on a JEOL PS-100 instrument at 100 MHz in CDCI3, C5D5N or CD3COCD3 with

TMS als internal standart. Merck silica gel (0.05 to 0.2 mm) was used for TLC.

Isolation of 1 and 3 The CHCI3 extract (6.0 g) was passed over silica

gel column. Elution with CHCls-MeOH (98:2) yielded 1 (118 mg). After recrystallization from aceton-ether colourless crystals were obtained. Further elution with CHCla-MeOH (93:7) leads to the isolation of 3 (800 mg) as crystals, which were recrystallized from acetone-ether.

Oxidation of 1 to 2 To a solition of 1 (50 mg) in pyridine (3 ml) was

treated with chromium trioxide (60 mg) at room temperature for 35 h. The reaction mixture was poured into water and extracted with chloroform. The usual treatment of the extract gave a crystalline product (2) (42 mg), which was recrystallized from acetone-dichlormethane to yield pure substance identical with teuscordinon (mixed m.p., IR and m NMR).

Acetylation of 3 The diol (3) (100 mg) was treated with acetic

anhydride (1.5 ml) and pyridine (2-3 drops) at room temperature overnight. The crude diacetate (96 mg) was purified by crystallization and recrystallization from CHCl3-Ether to give pure crystals, C24H26O9, m.p. 185-187 °C, vmax 1720-1740 (intensive) and 1240 cm-i , Ö 1.92 (3H, s, COOMe), 2.04 (3H, s, COOMe), 5.25 (1H, dd, J 4 and 12 Hz,. H-2), 5.20 (1H, t, J 3 Hz, H-6) and 2.98 (1H, dd, J 2.5 and 14.0 Hz, la-H) .

Jones oxidation of 3 to 5 To a solution of 3 (100 mg) in acetone was added

some drops of Jones reagent and the mixture was stirred for 10 min under ice-cooling. The mixture was added to cold aqueous sodium chloride and extracted with ether. The usual treatment of the extract gave a crystalline product (98 mg), which was recrystallized from methanol to yield pure substance, C20H20O7, m.p. 223-225 °C, m/e 372 (M+).

[1] G. Y. Papanov, P. Y. Malakov, and F. Bohlmann, Phytochemistry 20, 170 (1981).

[2] G. Y. Papanov and P. Y. Malakov, Z. Natur-forsch. 36b, 112 (1981).

[3] E. Fujita, I. Uchida, and T. Fujita, J. Chem. Soc. Perkin Trans. I 1974, 1574.

[4] I. Uchida, T. Fujita, and E. Fujita, Tetrahedron 31, 841 (1975).

[5] A. Chatterjee, A. Banerjee, and F. Bohlmann, ibid. 33, 2407 (1977).

[6] E. Gäcs-Baitz, L. Radics, G. B. Oganessian, and A. Mnatsakanian, Phytochemistry 17, 1967 (1978).

[7] The authors are grateful to Prof. Dr. F. Bohlmann (Institut für Organische Chemie der Technischen Universität Berlin-12) for recording of the *H NMR spectra.