Sesqui- and diterpenoids from two Japanese and three European liverworts

Phytochemistry 56 (2001) 347±352

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Sesqui- and diterpenoids from two Japanese and three European liverworts Fumihiro Nagashima, Yoshinori Asakawa * Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan Received 9 December 1999; accepted 29 March 2000 Dedicated to Professor Otto R. Gottlieb on the occasion of his 80th birthday

Abstract A new peroxy muurolane-type sesquiterpenoid was isolated from the ether extract of the Belgium liverwort Scapania undulata, together with three known ent-muurolanes. A new lepidozane-type sesquiterpenoid was isolated from the Japanese Porella subobtusa together with a known santalane- and two africane-type sesquiterpenoids. All structures were determined by means of NMR spectroscopic techniques. The chemosystematics of each species are discussed. # 2001 Elsevier Science Ltd. All rights reserved. Keywords: Scapania undulata; S. nemorea; Mylia taylorii; Porella subobtusa; Jungermannia truncata; Liverwort; Hepaticae; Muurolane-type; Lepidozane-type; Labdane-type; seco-Clerodane-type; Sesquiterpenoid; Diterpenoid; Chemosystematics

1. Introduction

2. Results and discussion

As part of a search for novel and biologically active compounds in the Hepaticae, we are continuing to study the chemical constituents of liverworts (Asakawa, 1982, 1995). Liverworts contain a large amount of mono-, sesqui- and diterpenoids, and aromatic compounds. In particular, liverworts contain pinguisane-type sesquiterpenoids, sacculatane-type diterpenoids and bis(bibenzyl) aromatic compounds which have not been found in higher plants. Chemical di€erences of the main components in the same liverwort species have been noted from di€erent localities (Asakawa, 1982, 1995; Nagashima and Asakawa, 1998). In this paper, we describe the isolation and characterization of new muurolane- and lepidozane-type sesquiterpenoids from Scapania undulata (L.) Dum. and Porella subobtusa (Steph.) Hatt., respectively. We report also the distribution of sesqui- and diterpenoids in three European liverworts S. undulata (L.) Dum., Scapnia nemorea (L.) Dum. and Mylia taylorii (Hook.) S. Gray, and two Japanese P. subobtusa (Steph.) Hatt. and Jungermannia truncata Nees and discuss their chemosystematics.

2.1. Scapania undulata

* Corresponding author. Tel.: +88-622-9611; fax: +88-655-3051. E-mail address: [email protected] u.ac.jp (Y. Asakawa).

A new peroxy sesquiterpenoid 1 was isolated from the ether extract of Belgian S. undulata, together with three previously known muurolanes, (+)-ent-epicubenol (Connolly et al., 1982), (+)-4-muurolen-6a-ol and entT-muurolol (Nagashima et al., 1994). The EIMS and HR±EIMS spectra of compound 1 produced the molecular formula C15H24O2 (anal. m/z 236.1763 [M]+) indicating four degrees of unsaturation. The 1H and 13C NMR spectra of 1 indicated the presence of three secondary methyls, a tertiary methyl, a trisubstituted double bond (C 129.9 d, 147.5 s) and two quaternary carbons (C 74.9, 77.7) bearing an oxygen atom. The 1H NMR spectrum of 1 resembled the spectra of muurolanes 2±4. The above spectral data suggested that compound 1 might be a muurolane-type tricyclic sesquiterpenoid. The 1H±1H COSY spectrum of 1 indicated the presence of two partial structures A and B (Fig. 1). The HMBC spectrum (Fig. 1) displayed the cross peak between the tertiary methyl proton (H-15) and a methylene carbon (C-3) in the partial structure A, a quaternary carbon at  74.9 (C-4), and an ole®nic carbon at  129.9 (C-5). The ole®nic proton (H-5) was correlated with a methine carbon (C-7) in the partial

0031-9422/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S0031-9422(00)00220-X

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structure B and a quaternary carbon at  77.7 (C-1), which also correlated with a secondary methyl (H-14) in the partial structure B and a methylene carbon (C-2) in the partial structure A. Additionally, the chemical shifts of two quaternary carbons (C 74.9, 77.7) bearing an oxygen atom of compound 1 appeared lower than that of compounds 2 ( 72.7) and 6 ( 67.7). The IR spectrum of 1 showed neither absorption bands of hydroxyl nor carbonyl group. The existence of two oxygen atoms by HR±EIMS and the above spectral data supported the presence of a peroxy group in the structure of 1. Thus,

the structure of 1 was established to be a 1,4-peroxy muurolane-type sesquiterpenoid. This planar structure accorded with 5 isolated from Bazzania tricrenata (Buchanan, 1994), Bazzania trilobata (Nagashima et al., 1996b) and Illicium tsangii (Ngo et al., 1999). However, the 1H and 13C NMR spectra of 1 were not slightly identical with those of 5, indicating that compound 1 might be a stereoisomer of 5. In the phase sensitive NOESY spectrum of 1, the NOEs were observed between (i) H-14 and H-9a, H-9b, and H-2b, (ii) H-10a and H-2a, (iii) H-4b and H-3b, H-6, and (iv) H-8b and H-9b, H-12. The stereochemistry of the secondary methyl (H-14) and isopropyl group at C-7 was revealed to be trans, but the stereochemistry of the 1,4-peroxy group remains to be clari®ed. From the above spectral evidence, the structure of 1 was deduced to be 1,4-peroxy-5-muurolene to take account of the isolation of muurolane-type sesquiterpenoids 2±4 from this species. 2.2. Porella subobtusa

Fig. 1. 1H±1H correlations (bold lines) and HMBC correlations (arrows) of 1.

A new lepidozane-type sesquiterpenoid 7 was isolated from the ether extract of the Japanese P. subobtusa, together with three known sesquiterpenoids, a-santalane-12(S),13-diol (Toyota et al., 1992; Nagashima et al., 1996a), caespitenone (Tori et al., 1993) and secoswartzianin B (Tori et al., 1994). The molecular formula, C16H28O (anal. m/z 236.2143 [M]+), of 7 was determined by HR±EIMS. The IR spectrum had no absorption for hydroxyl and carbonyl

F. Nagashima, Y. Asakawa / Phytochemistry 56 (2001) 347±352

groups. The 1H NMR spectrum showed the presence of a secondary methyl, an ole®nic methyl, two tertiary methyls, a methoxyl group and an ole®nic proton, together with two cyclopropane protons ( 0.15, ±0.14 each 1H). The 13C NMR spectrum of 7 contained sixteen carbons and its DEPT spectrum showed the presence of a trisubstituted ole®nic carbon and a methine bearing a methoxyl group, together with ®ve methyls, four methylenes, three methines and a quaternary carbon. The 1H and 13C NMR spectra of 7 resembled those of (4S*, 5S*, 6R*, 7R*)-1(10)E-lepidozen-5-ol (8) (Tori et al., 1993) except for the presence of a methoxyl group. Accordingly, the structure of 7 was recognized to be a lepidozane-type sesquiterpenoid. The 1H±1H COSY spectrum gave the connectivity of ÿCH(1)ÿCH2(2)ÿCH2(3) ÿCH(CH3)(4)ÿCH(5)ÿCH(6)ÿCH(7)ÿCH2(8)ÿCH2(9)ÿ. The HMBC spectrum showed the correlation between (i) H-14Me and C-1, C-9, and (ii) H-12Me, H-13Me and C-6, C-7, C-11. Thus, the structure of 7 was determined to be a lepidozane-type sesquiterpenoid with a methoxyl group at C-5. The NOESY spectrum showed NOE correlations between (i) H-7 and H-8a, H-13, (ii) H-13 and H-5, (iii) H-6 and H-8b, H-12, H-15, methoxyl group at C-5, and (iv) H-1 and H-4, H-9a. On the basis of the above evidence, the structure of 7 was determined to be (4S*, 5S*, 6R*, 7R*)-5-methoxy-1(10)E-lepidozene. 2.3. Scapania nemorea, Mylia taylorii and Jungermannia truncata ent-Spathulenol (Asakawa et al., 1980) and (ÿ)diplophyllin (Ohta et al., 1977), and a seco-clerodanetype diterpenoid 9 were isolated from the ether extract of the German species S. nemorea. The 1H NMR spectrum of 9 was identical with that of the methyl ester derivative of 10 isolated from Pulicaria angustifolia (Compositae) (Singh et al., 1985). However, the 13C NMR data of 9 were not reported in the reference, therefore, its NMR assignment was determined by the HMQC and HMBC spectra (Table 2). In addition, compound 9 was isolated for the ®rst time from S. nemorea as a natural product. Trinorsesquiterpene 11 (El-Seedi et al., 1994), (+)(9R*, 13S*)-dihydroxy-8(17),14-labdadiene (Nagashima et al., 1997) and 13-epi-sclareol (Bigley et al., 1960) were isolated from the ether extract of the Japanese species J. truncata. The 1H NMR spectrum of 11 was identical with the reference data (El-Seedi et al., 1994). Furthermore, chiral GC-MS analysis indicated that 11 was composed of a mixture of both enantiomers (ca.1:1). The ether extract of the Austrian species M. taylorii a€orded ten sesquiterpenoids, (+)-ent-maali-4(15)-en1b-ol, cyclomyltaylenol, myltaylenol, (+)-globulol, (+)4(15)-dehydroglobulol, (+)-4(15)-dehydroledol, (ÿ)-myliol, (ÿ)-taylorione, myltaylorione A and myltaylorione B (Matsuo and Takaoka, 1990; Takaoka et al., 1991).

349

The chemical constituents of S. undulata collected in di€erent locations have been analyzed and the muurolane- and longibornane-type sesquiterpenoids or labdane-type diterpenoids isolated as main components (Huneck and Klein, 1967; Matsuo et al., 1973; Connolly et al., 1982; Huneck et al., 1986; Nagashima et al. 1993; Nagashima et al., 1994; Yoshida et al., 1997). The present species produced the muurolane-type sesquiterpenoids as the main components and, therefore, this species is classi®ed into the muurolane-type. The chemical constituents of S. nemorea have already been analyzed. Bibenzyls (Gorham, 1977), aromadendrane- and longifolene-type sesquiterpenoids (Svenson and Bendz, 1972; Andersen et al., 1978) and seco-clerodane- and cis-clerodane-type diterpenoids (Geis et al., 1999) were isolated. The isolation of an eudesmanetype sesquiterpenoid was the ®rst example from S. nemorea. The labdane-type diterpenoids were obtained from J. truncata as main components. In the previous study of the same species (Nagashima et al., 1990; Buchanan et al., 1996; Liu et al., 1997; Nagashima and Asakawa, 1998), the ent-kaurane-type diterpenoids were isolated as major components. Thus, the present species is considered to be a new chemo-type of J. truncata. The chemical constituents of the present P. subobtusa and M. taylorii are no geographical di€erence in each same species. 3. Experimental 3.1. General 1

H and 13C NMR: 400 and 600 MHz (1H NMR) and 100, 150 MHz (13C NMR). Chemical shift values were expressed in  (ppm) down®eld from tetramethylsilane as an internal standard (1H NMR) and  77.03 (ppm) from CHCl3 as a standard (13C NMR). TLC: visualized under UV (254 nm) light and by spraying with Godin reagent (Godin, 1954) followed by heating. MeOH± CH2Cl2 (1:1) and CHCl3 were used for Sephadex LH-20 and [a]D, respectively. 3.2. Plant material S. undulata (L.) Dum. (JH3853) was collected in Belgium and identi®ed by Professor S.R. Gradstein (UniversitaÈt GoÈttingen, Germany). S. nemorea (L.) Dum. (N9607) and M. taylorii (Hook.) S. Gray (N9608) were collected in Germany and in Salzburg, Austria, respectively and identi®ed by Dr. S. Huneck (Germany). P. subobtusa (Steph.) Hatt. (H9501) and J. truncata Nees (N9304) were collected in Tokushima, Japan and identi®ed by Dr. M. Mizutani (Hattori Botanical Lab., Japan). The voucher specimens were deposited at

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Faculty of Pharmaceutical Sciences, Tokushima Bunri University. 3.3. GC±mass spectrum The temperature programming of GC±MS analysis performed from 50 C isothermal for 3 min, then 50± 250 C at 5 C minÿ1, and ®nally isothermal at 250 C for 15 min and from 80±250 C at 15 C minÿ1, and ®nally isothermal at 250 C for 15 min. Injection temp was 250 C. A fused silica column coated with b-DEX 120 (30 m0.25 mm id, ®lm thickness 0.25 mm) and DB1 (30 m0.25 mm id, ®lm thickness 0.25 mm) were used. 3.4. Extraction and isolation from Scapania undulata The dry material (425 g) of S. undulata was ground and extracted with Et2O for 1 month. The crude extract (4.9 g) was divided into 11 fractions by CC on silica gel using n-hexane-EtOAc gradient. Fr. 5 was chromatographed on SiO2 and MPLC (Lobar1 column) to give (+)-ent-epicubenol (640 mg) and a sesquiterpene mixture, which was rechromatographed on SiO2 and prep. HPLC (Chemcosorb 5-ODS-H, CH3CN) to yield compound 1 (5 mg) and (+)-4-muurolen-6a-ol (35 mg). (+)-T-muurolol (16 mg) and (+)-ent-epicubenol (116 mg) were isolated by chromatography on Sephadex LH20 (CH2Cl2±MeOH 1:1), SiO2 and prep. HPLC (Chemcosorb 5-ODS-H, CH3CN) of Fr. 6. A fatty acid mixture from Fr. 7 was treated with N,O-bis(trimethylsilyl)acetamide to obtain TMS derivatives which were analyzed by GC±MS to detect palmitic acid, linoleic acid, linolenic acid and octadecanoic acid. 3.5. Compound 1 Amorphous; [a]D +41.9 (c 2.30); HR±EIMS: found 236.1763 C15H24O2 requires 236.1776; FTIR nmax cmÿ1: 1458, 1375, 1255, 900, 878, 764; 1H and 13C NMR: Tables 1 and 2; EIMS m/z (rel. int.): 236[M]+(17), 218 (46), 204 (37), 200 (56), 193 (33), 185 (32), 175 (100), 159 (70), 157 (81), 147 (33), 143 (51), 128 (26), 115 (21), 105 (35), 91 (28), 77 (15), 67 (8), 55 (11), 43 (19). 3.6. Extraction and isolation from Porella subobtusa The ether extract (4.3 g) from dried P. subobtusa (93 g) was divided into 10 fractions by CC on silica gel using n-hexane±EtOAc gradient. Frs. 5 and 6 were chromatographed on SiO2, MPLC (Lobar1 column, Si 60) and prep. HPLC (Nucleosil 50-5, 10% n-Hexane± EtOAc) to give (4S*, 5S*, 6R*, 7R*)-5-methoxy-1(10)Elepidozene (7) (8 mg), caespitenone (57 mg) and secoswartzianin B (11 mg). a-Santalane-12(S),13-diol (368 mg) was isolated from Fr. 8 by chromatography on Sephadex LH-20, SiO2 and MPLC (Lobar1 column).

Table 1 1 H NMR data of 1 and 7 (600 MHz, CDCl3) H

1

1 2

1.27 ddd (13.2, 12.1, 4.1), a 2.35 ddd (13.2, 9.6, 3.8), b 1.50±1.56 m, a 2.01 ddd (13.2, 9.6, 3.8), b

3 4 5 6 7 8

6.09 d (1.9)

9 10 11 12 13 14 15 OCH3 a

2.51 q like 1.34 m, a 1.77 m, b 1.50±1.56 m, a 1.45 dddd (13.2, 13.2, 11.3, 4.7), b 1.73 m 1.90 oct. (6.9) 0.82 3H, d (6.9)a 0.89 3H, d (6.9)a 1.03 3H, d (7.1) 1.36 3H, s

7 5.38 br s 1.83 br q 2.14 br s 1.10±1.17 m 1.70 br t 1.60 m 2.72 dd (8.2, 1.9) 0.15 dd (8.2, 6.0) ÿ0.14 dd (10.2, 5.5) 1.10±1.17 m 1.98 m 1.96 m 2.30 br d (12.9) 1.06 3H, s 1.00 3H, s 1.01 3H, d (7.1) 1.59 3H, s 3.29 3H, s

May be interchanged in the same column.

3.7. (4S*, 5S*, 6R*, 7R*)-5-Methoxy-1(10)E-lepidozene (7) [a]D ÿ75.2 (c 2.10); GC±HRMS: found 236.2143 C16H28O requires 236.2141; FTIR nmax cmÿ1: 1450, 1377, 1190, 1151, 1093, 918; 1H and 13C NMR: Tables 1 and 2; GCMS m/z (rel. int.): 236 [M]+(6), 221 (1), 204 (16), 189 (21), 165 (47), 161 (31), 152 (26), 151 (18), 135 (26), 133 (20), 125 (100), 122 (69), 112 (86), 107 (57), 93 (75), 91 (32), 85 (45), 82 (57), 79 (35), 73 (80), 69 (20), 67 (41), 55 (30), 53 (18), 41 (35). 3.8. Extraction and isolation from Scapanea nemorea The ether extract (1.5 g) from dried S. nemorea (52 g) was chromatographed on silica gel using n-hexaneEtOAc gradient to give seven fractions. Fr. 3 was rechromatographed on SiO2 and prep. HPLC (Nucleosil 50±5, 10% n-hexane±EtOAc) to yield ent-spathulenol (7 mg) and diplophyllin (9 mg). Fr. 4 was also chromatographed on Sephadex LH-20 and SiO2 to give diplophyllin (10 mg). 5,10-seco-Clerodane-type diterpene 9 (7 mg) was isolated from Fr. 5 by chromatography on Sephadex LH-20 and SiO2. 3.9. Compound 9 [a]D +200.9 (c 2.30); HR±EIMS: found 344.1989 C21H28O4 requires 344.1987; FTIR nmax cmÿ1: 1780, 1750, 1715, 1250; UV lmaxnm (log ): 209 (4.22), 242 (3.27, sh) (c 1.0610ÿ4, EtOH); 1H NMR (600 MHz):  5.28 (1H, dddd, J=12.4, 12.4, 4.1, 1.9 Hz, H-1), 5.96

F. Nagashima, Y. Asakawa / Phytochemistry 56 (2001) 347±352 Table 2 13 C NMR data of 1, 7 and 9 (150 MHz, CDCl3) C

1

7

9

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 OCH3 COOCH3

77.7 27.1 30.0 74.8 129.8 147.4 42.9 22.8 28.0 37.2 32.3 18.1a 20.6a 14.5 21.7

126.7 24.8 30.6 34.3 84.7 34.8 26.3 28.0 39.0 134.7 18.6 21.5 23.1 20.1 17.0

126.6 128.4 140.7 136.9 144.8 33.8 29.2 35.5 37.8 35.6 34.7 23.6 170.9 115.2 174.0 73.0 13.8 166.6 118.1 18.5

a

56.2

52.1

May be interchanged in the same column.

(1H, ddd, J=11.8, 2.7, 1.6 Hz, H-2), 7.25 (1H, dd, J=4.7, 2.5 Hz, H-3), 2.63 (1H, br d, H-6a), 2.10 (1H, ddd, J=13.7, 13.7, 2.5 Hz, H-6b), 0.85 (1H, m, H-7a), 1.52 (1H, m, H-7b), 1.40 (1H, m, H-8), 1.72 (1H, d quint., J=13.5, 1.9 Hz, H-10a), 2.29 (1H, t, J=13.5 Hz, H10b), 1.48 (1H, m, H-11), 1.55 (1H, m, H-11), 2.38 (2H, t like, J=7.7 Hz, H-12), 5.86 (1H, quint., J=1.6 Hz, H14), 4.76 (2H, d, J=1.6 Hz, H-16), 0.78 (3H, d, J=6.6 Hz, H-17), 4.85 (1H, br s, H-19), 5.08 (1H, t, J=1.9 Hz, H-19), 0.72 (3H, s, H-20); 13C NMR: Table 2; EIMS m/ z (rel. int.): 344[M]+(27), 312 (37), 297 (13), 285 (11), 269 (4), 255 (5), 247 (7), 215 (13), 201 (15), 187 (13), 173(28), 163 (24), 159 (37), 145 (41), 131 (70), 119 (47), 117 (36), 115 (23), 111 (44), 107 (30), 105 (82), 98 (40), 93 (30), 91 (100), 79 (40), 77 (44), 67 (24), 55 (32), 41 (35). 3.10. Extraction and isolation from Jungermannia truncata and Mylia taylorii The ether extract (1.3 g) of J. truncata was chromatographed on silica gel using n-hexane±EtOAc gradient to give nine fractions. The GC±MS of Fr. 1 showed the presence of cuparene. Compound 11 ([a]D +3.3 , c 1.28) (3 mg) was puri®ed by chromatography on Sephadex LH-20, SiO2 and prep. TLC. Fr. 5 was rechromatographed on SiO2 to give stigmasterol (14 mg) and (+)(9R*, 13S*)-dihydroxy-8(17),14-labdadiene (5 mg). The CC on Sephadex LH-20, SiO2, MPLC (Lobar1 column, Si 60) gave a mixture including 13-epi-sclareol which was recrystallized from n-hexane±EtOAc to a€ord the pure compound (96 mg).

351

The ether extract (2.8 g) from M. taylorii (79 g) was divided into 9 fractions by CC on silica gel using nhexane±EtOAc gradient. Fr. 4 was rechromatographed on Sephadex LH-20, SiO2, MPLC (Lobar1 column, Si 60) and prep. HPLC (Nucleosil 50-5, 10% n-hexane± EtOAc) to give (ÿ)-taylorione (127.5 mg), myltaylorione A (4 mg) and myltaylorione B (2 mg) were isolated. Fr. 5 was rechromatographed on Sephadex LH-20 to give a mixture including myliol which was recrystallized from n-hexane to give (ÿ)-myliol (254 mg) and mother liquid which was rechromatographed on MPLC (Lobar1 column, Si 60 or CN) and prep. HPLC (Chemcosorb 5-ODS-H, CH3CN) to yield (+)-ent-maali4(15)-en-1b-ol (14 mg), cyclomyltaylenol (25 mg), (+)4(15)-dehydroledol (5 mg) and (ÿ)-taylorione (9 mg). The CC on Sephadex LH-20, SiO2, MPLC (Lobar1 column, Si 60) and prep. HPLC (Chemcosorb 5-ODSH, CH3CN) of Fr. 6 gave myltaylenol (10 mg), (+)globulol (4 mg) and (+)-4(15)-dehydroglobulol (5 mg). Acknowledgements We thank Dr. M. Mizutani (Hattori Bot. Laboratory, Japan) and Professor S.R. Gradstein (UniversitaÈt GoÈttingen, Germany) for the identi®cation, Dr. S. Huneck (Germany) for the collection and identi®cation of the species. Thanks are also due to Dr. T. Hashimoto for the collection of the liverwort, Dr. M. Tanaka (TBU) and Miss. Y. Okamoto (TBU) for measurements of 600 MHz NMR and mass spectra, and Mr. T. Uematsu, Miss. A. Mise, Miss. N. Matsumura and Miss. K. Yamada for their technical assistance. References Andersen, N.H., Ohta, Y., Moore, A., Tseng, C.W., 1978. Anastreptene, a commonly encountered sesquiterpene of liverworts (Hepaticae). Tetrahedron 34, 41±46. Asakawa, Y., 1982. Chemical constituents of Hepaticae. In: Herz, W., Grisebach, H., Kirby, G.W. (Eds.), Progress in the Chemistry of Organic Natural Products. Springer, Vienna, vol. 42, pp. 1±285. Asakawa, Y., 1995. Chemical constituents of the Bryophytes. In: Herz W., Kirby G.W., Moore R.E., Steglich W., Tamm Ch. (Eds.), Progress in the Chemistry of Organic Natural Products. Springer, Vienna, vol. 65, pp. 1±618. Asakawa, Y., Inoue, H., Toyota, M., Takemoto, T., 1980. Sesquiterpenoids of fourteen Plagiochila species. Phytochemistry 19, 2623± 2626. Bigley, D.B., Rogers, N.A.J., Barltrop, J.A., 1960. Synthesis of diterpenes. Part III. The synthesis, and con®guration at position 13, of diterpenes of the labdane group. Journal of Chemical Society, 4613± 4627. Buchanan, M.S., 1994. Natural products from the Hepaticae. Doctor thesis. The University of Glasgow, pp. 1±171. Buchanan, M.S., Connolly, J.D., Kadir, A.A., Rycroft, D.S., 1996. Sesquiterpenoids and diterpenoids from the liverwort Jungermannia truncata. Phytochemistry 42 (6), 1641±1646. Connolly, J.D., Phillips, W.R., Huneck, S., 1982. (+)-ent-Epicubenol from the liverwort Scapania undulata. Phytochemistry 21 (1), 233±234.

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