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Sesquiterpene alcohols from Gonospermum fructicosum
%500+0.00 00319422/92 si’, 1992PrrgamonPressplc
Phyrochemisrry.Vol 31. No. 5, pp 1816 1X17. 1992
Prmtedm Great Britam
SESQUITERPENE
ALCOHOLS
GONOSPERMUM
FROM
FRUCTICOSUM
ANTONIO G. GONZALEZ, JAIME BERMEJ~ BARRERA,* JORGE TRIANA MI?NDEZ,+ MARIANA LOPEZ SANcHEzt Josh L. EIROA MARTiNEzt
and
Centro de Productos
Naturales Org&mcos Antonio GonzBlez. Consejo Superior de Investigaciones Cientificas, Carretera La Esperanza 2. La Laguna. 38206 Tenerlfe, Canary Islands, Spain; tDepartamento de Quimica Universidad de Las Palmas de Gran Canana, Tafit’a, Las Palmas, Canary Islands, Spain (Recen>ed 17 June 1991) Key Word Index
Gonospermumfructrcosum;
Anthemidae: sesquiterpene alcohols; hydroxycostol.
Abstract-The aerial part of Gonospermumfructicosum compounds. The structures of the new compounds hydroxycostol and 3a-hydroxycostol by spectroscopic
yielded three new sesquiterpene alcohols as well as four known were established as 4a-hydroxy-48-methyldihydrocostol, l/Iand chemical means.
INTRODUCTION
The genus Gonospermum, consisting of four species endemic to the Canary Islands, is distributed over the more westerly islands. We report the isolation and identification of three new sesquiterpene alcohols together with four known compounds. RESC‘LTS AND DISCUSSION
An extract of the aerial part of Gonospermum fructicosum (Buch.) Less afforded p-sitosterol, /?-sitosterol+Dglucoside, the coumarins scoparone and scopoletin, and three new sesquiterpenes, l-3. The structure of 1 could be deduced from its ‘H NMR spectrum (Table 1) which had signals for an angular methyl group and one other methyl group, but none for a gem-hydroxyl. This fact, taken together with the’hydroxyl bands visible in the IR spectrum, indicated a tertiary hydroxyl group which was borne out by the presence in the 13C NMR spectrum of signals for a methyl singlet at 6 1.09 (Me-4) (Table 1) and a quaternary carbon at 672.2 (C-4) (see Experimental). The other hydroxyl group must be primary as acetylation of 1 gave the mono-acetate la with a paramagnetic shift of 0.46 ppm from the ‘H NMR signals recorded for the group of 1. Oxidation of 1 and. correlation with the known compounds lb-d [l, 21 further confirmed the structure and stereochemistry of 1. The ‘H NMR spectrum of 2 (Table 1) partly resembled that of 1, differing in that it had no signals for the Me-4 while there were signals for an exocyclic methylene at 6 4.70 and 4.50. The /?-orientation of the C-l hydroxyl group was deduced from the coupling constant [3]. Diacetate 2a was obtained when 2 was acetylated, showing that there were two hydroxyl groups in the molecule. Treatment of 2 with Jones’ reagent afforded 2b, which was methylated with diazomethane to give 2c with spectroscopic data in agreement with those given in ref. [4]. The ‘H NMR spectrum of 3 (Table 1) was close to that of 2 but with the hydroxyl, group sited at C-3 and the *Author to whom correspondence should be addressed,
5%
,1’1’ RI
;
R
1
R= CH&H
Id
lb COOMe
2 2a 2b 2c
R= CbOH ; R,=OH R= CH$Ac; R,= oAc R= COOH , R,= OH R= COOMe; R,= OH
3 3a
R= t&OH ; R,= OH R= CH$Ac; R,= OAc
geminal proton was seen as a triplet at 64.23 indicating an allylic position. The a-orientation of the C-l hydroxyl group could be deduced from the relatively small coupling constant [S, 61. The similarity of the signals of 2 and 3 in other respects indicated that 3a-hydroxycostol was also to be found in the plant. Evidence of there being two hydroxyl groups in this molecule was provided when a diacetate, 3a, was obtained by treating 3 with Ac,O-pyridine. EXPERIMENTAL Mps: uncorr; ‘H NMR: 200 MHz, CDCI,; MS: direct inlet, 70 eV; CC: silica gel (0.2-W mm). PIant material. The aerial part of Gonospermum fiucticosum
was collected at Taganana, Tenerife in May 1989 and a voucher specimen was filed with the Herbarium of the Viera y Clavijo Botanical Gardens in Gran Canana. Extraction andchromatography. The air-dried plant material (2 kg) was finely ground and extracted with hot EtOH. After filtration and removal of the EtOH in uacuo, the residue (777 g) was subjected to CC with mixtures of hexane-EtOAc of increasing polarity, to give the following substances: (9:1), /?-sitosterol
1816
Short Reports
1817
Table 1. ‘H NMR spectral data of compounds 1, la, 2, 2a, 3 and 3a (200 MHz, CDCI,, TMS as int. stand.) H
1
1
-
3 5
-
12 13 13’ 14 15 15’ OAc
4.12 s 5.00 d (1.4) 4.90 d (1.0) 0.88 s 1.09 s --
la
2
2a
3
3a
4.70 dd (4.7, 11.7) 2.32 dddd (2.5, 12.5) 4.57 s 5.05 s 5.00 s 0.78 s 4.78 s 4.51 s 2.08 s 2.05 s
4.23 t (2.8) 2.30 br d (12.5) 4.08 s 4.99 s 4.87 s 0.66 s 4.87 s 4.51 s
5.34 t (2.8) 2.25 m
4.58 s 5.03 s 5.00 s 0.89 s 1.11 s _ 2.09 s
3.43 dd (4.5, 11.5) _ 2.31 dddd (2.5, 12.5) 4.15 s 5.05 s 4.95 s 0.71 s 4.76 s 4.50 s -
4.58 s 5.06 s 5.01 s 0.73 s 5.06 s 4.68 s 2.09 s 2.05 s
Values in parentheses are coupling constants in Hz.
(50 mg) and (2:1), scoparone (10 mg). Re-chromatography (C,H,-EtOAc, 1: 1) of the fractions eluted with hexane-EtOAc (1:l) and purification by TLC (C,H,-EtOAc) afforded, in order: scopoletin (8 mg), l(l90 mg), 2 (100 mg), and 3 (90 mg) while the most polar fractions yielded p-sitosterol-/%D-glucoside (130 mg). 4a-Hydroxy-4P-methyldi~ydrocostol (I). C15Hj602. needles. mp 192-193” (hexane-EtOAc); IR ~2:‘~ cm-‘: 3575,3380,1630, 1160, 1080, 1005, 895; MS m/z (rel. int.): 238 [M]’ (2), 220 [M -H,O]+ (13), 202 [M-2H,O]+ (15), 187 [M-2H,O-Me]’ (15), 162 (41), 135 (71), 81(58), 71 (69); ‘H NMR: see Table 1; 13C NMR(CDCI,;C-1-C-15): 842.15,20.12,43.46,72.19,55.0,27.32, 41.09,26.59,44.71,34.66,154.11,65.26,107.89, 18.68,22.70(some signals may be interchangeable). Acetylation of compound 1. Compound 1 was acetylated with Ac,O-pyridine for 12 hr and usual work-up gave the acetate la: C 17H 280 3, gum; IR v:::‘~ cm-‘: 3500, 1750, 1700, 1280, 1130, 850; MS m/z (rel. mt.): 280 [M]’ (4), 262 [M -H,O]’ (6), 220 [M-HOAc]+ (15), 187(19), 177(28), 151(48),81(55),69(86). ‘H NMR: see Table 1. Oxidation ofcompound 1. Compound l(l30 mg) was dissolved in Me&O (30 ml) and cooled in ice. While the mixture was continually stirred, Jones’ reagent was added in drops to slight excess. The mixture was stirred for a further 5 min then excess reagent was removed with MeOH, the mixture was extracted and the solvent evapd to dryness. The residue was subjected to TLC (hexane-EtOAc, 1:l) to give lb (60 mg); ‘H NMR data identical to those given in ref. [l]. Treatment of lb with excess jones’ reagent for 4 hr at room temp. afforded lc (40 mg); ‘H NMR data identical to those in the lit. [2]. Methylabion of compound lc. Compound lc (40 mg) was dissolved in Et,0 and CH,N, was added to give Id (30 mg); ‘H NMR data identical to those given in ref. [2]. lb-Hydroxycostol (2). C 15H 240 a, needles, mp 149-150 (hex_EtOAc). IR ~2:” cm-‘: 3560,3360, 1630, 1430,880, SSO, MS m/z (rel. int.): 236 [M]’ (4), 218 [M-H,O]+ (17), 200 [M -2H,O]+ (15), 185 [M-2H,O-Me]+ (18), 159 (40), 107 (46), 95 (48), 91 (73); ‘H NMR: see Table 1. Acetylation of compound 2. Compound 2 (20 mg) was acetylated as described for 1, giving 2a (25 mg) as an oil, C,,HZsO,; IR
VCHcl, ntax
cm-‘: no hydroxy band, 1720,1630,1425,1240,1015,885, MS m/z (rel. int.): 320 [M]’ (l), 260 [M-HOAc]’ (17), 200 [M -2HOAcl” (lOO), 185 [M-2HOAc-Me]’ (81), 157 (58), 91 (59); ‘H NMR: see Table 1. Oxidation ofcompound 2. Compound 2 (50 mg) was oxidized as described for 1, giving 2b (25 mg). Treatment of 2b with CHzCl, m Et,0 gave 2c (20 mg); ‘H NMR data identical to those already reported [4]. 3a-Hydroxycostol(3). C15HZ402, gum; IR ~2:‘~ cm-‘: 3560, 3380, 1630, 1440, 1360, 1130, 1080, 890, MS m/z (rel. int.): 236 [M]‘(7),218[M-H,0]+(10),203[M-H,O-Me]+(10),133 (33), 107 (40), 91 (49), 60 (88); ‘H NMR: see Table 1. Acetylation 0s compound 3. Acetylation of 3 (30 mg) in A@-pyridine for 24 hr and usual work-up gave the acetate 3a: Cl,H,,O,, gum; IR v%:‘~ cm-‘: 1720, 1630, 1360, 1240, 1020, 910, 890, MS m/z (rel. int.): 320 [M]’ missing 260 [M -HOAc]+ (7), 200 [M-2HOAc]+ (17), 185 [M-2HOAc -Me]+ (17), 177 (43), 171 (47), 117 (67), 98 (90); ‘H NMR: see Table 1. Acknowledgements-This work has been partly financed by a grant from CICYT (PB88-0049). AGG is indebted to the AIETI Foundation, Madrid.
REFERENCES 1. Bohhnann, F., Ates, N. and Jakupovic, J. (1983) Phybochemistry 22, 1159. 2. Sanz., J. F., Castellano, G. and Marco, J. A. (1990) Phytochemistry 29, 541. 3. Bohhnann, F., Jakupovic, J., King, R. M. and Robinson, H. (1981) Pkytochemistry 20, 1613. 4. Van Hijfte, L. and Vandewalle, M. (1982) Tetrahedron Letters X3,2229. 5. Herz,, W., Subramanian, P. S. and Gelssman, T. A. (1968) J. Org. Chem. 10, 3743. 6. Ahmed, A. A. and Jakupovic, J. (1990) Phytochemistry 29, 3658.
Phyrochemisrry.Vol 31. No. 5, pp 1816 1X17. 1992
Prmtedm Great Britam
SESQUITERPENE
ALCOHOLS
GONOSPERMUM
FROM
FRUCTICOSUM
ANTONIO G. GONZALEZ, JAIME BERMEJ~ BARRERA,* JORGE TRIANA MI?NDEZ,+ MARIANA LOPEZ SANcHEzt Josh L. EIROA MARTiNEzt
and
Centro de Productos
Naturales Org&mcos Antonio GonzBlez. Consejo Superior de Investigaciones Cientificas, Carretera La Esperanza 2. La Laguna. 38206 Tenerlfe, Canary Islands, Spain; tDepartamento de Quimica Universidad de Las Palmas de Gran Canana, Tafit’a, Las Palmas, Canary Islands, Spain (Recen>ed 17 June 1991) Key Word Index
Gonospermumfructrcosum;
Anthemidae: sesquiterpene alcohols; hydroxycostol.
Abstract-The aerial part of Gonospermumfructicosum compounds. The structures of the new compounds hydroxycostol and 3a-hydroxycostol by spectroscopic
yielded three new sesquiterpene alcohols as well as four known were established as 4a-hydroxy-48-methyldihydrocostol, l/Iand chemical means.
INTRODUCTION
The genus Gonospermum, consisting of four species endemic to the Canary Islands, is distributed over the more westerly islands. We report the isolation and identification of three new sesquiterpene alcohols together with four known compounds. RESC‘LTS AND DISCUSSION
An extract of the aerial part of Gonospermum fructicosum (Buch.) Less afforded p-sitosterol, /?-sitosterol+Dglucoside, the coumarins scoparone and scopoletin, and three new sesquiterpenes, l-3. The structure of 1 could be deduced from its ‘H NMR spectrum (Table 1) which had signals for an angular methyl group and one other methyl group, but none for a gem-hydroxyl. This fact, taken together with the’hydroxyl bands visible in the IR spectrum, indicated a tertiary hydroxyl group which was borne out by the presence in the 13C NMR spectrum of signals for a methyl singlet at 6 1.09 (Me-4) (Table 1) and a quaternary carbon at 672.2 (C-4) (see Experimental). The other hydroxyl group must be primary as acetylation of 1 gave the mono-acetate la with a paramagnetic shift of 0.46 ppm from the ‘H NMR signals recorded for the group of 1. Oxidation of 1 and. correlation with the known compounds lb-d [l, 21 further confirmed the structure and stereochemistry of 1. The ‘H NMR spectrum of 2 (Table 1) partly resembled that of 1, differing in that it had no signals for the Me-4 while there were signals for an exocyclic methylene at 6 4.70 and 4.50. The /?-orientation of the C-l hydroxyl group was deduced from the coupling constant [3]. Diacetate 2a was obtained when 2 was acetylated, showing that there were two hydroxyl groups in the molecule. Treatment of 2 with Jones’ reagent afforded 2b, which was methylated with diazomethane to give 2c with spectroscopic data in agreement with those given in ref. [4]. The ‘H NMR spectrum of 3 (Table 1) was close to that of 2 but with the hydroxyl, group sited at C-3 and the *Author to whom correspondence should be addressed,
5%
,1’1’ RI
;
R
1
R= CH&H
Id
lb COOMe
2 2a 2b 2c
R= CbOH ; R,=OH R= CH$Ac; R,= oAc R= COOH , R,= OH R= COOMe; R,= OH
3 3a
R= t&OH ; R,= OH R= CH$Ac; R,= OAc
geminal proton was seen as a triplet at 64.23 indicating an allylic position. The a-orientation of the C-l hydroxyl group could be deduced from the relatively small coupling constant [S, 61. The similarity of the signals of 2 and 3 in other respects indicated that 3a-hydroxycostol was also to be found in the plant. Evidence of there being two hydroxyl groups in this molecule was provided when a diacetate, 3a, was obtained by treating 3 with Ac,O-pyridine. EXPERIMENTAL Mps: uncorr; ‘H NMR: 200 MHz, CDCI,; MS: direct inlet, 70 eV; CC: silica gel (0.2-W mm). PIant material. The aerial part of Gonospermum fiucticosum
was collected at Taganana, Tenerife in May 1989 and a voucher specimen was filed with the Herbarium of the Viera y Clavijo Botanical Gardens in Gran Canana. Extraction andchromatography. The air-dried plant material (2 kg) was finely ground and extracted with hot EtOH. After filtration and removal of the EtOH in uacuo, the residue (777 g) was subjected to CC with mixtures of hexane-EtOAc of increasing polarity, to give the following substances: (9:1), /?-sitosterol
1816
Short Reports
1817
Table 1. ‘H NMR spectral data of compounds 1, la, 2, 2a, 3 and 3a (200 MHz, CDCI,, TMS as int. stand.) H
1
1
-
3 5
-
12 13 13’ 14 15 15’ OAc
4.12 s 5.00 d (1.4) 4.90 d (1.0) 0.88 s 1.09 s --
la
2
2a
3
3a
4.70 dd (4.7, 11.7) 2.32 dddd (2.5, 12.5) 4.57 s 5.05 s 5.00 s 0.78 s 4.78 s 4.51 s 2.08 s 2.05 s
4.23 t (2.8) 2.30 br d (12.5) 4.08 s 4.99 s 4.87 s 0.66 s 4.87 s 4.51 s
5.34 t (2.8) 2.25 m
4.58 s 5.03 s 5.00 s 0.89 s 1.11 s _ 2.09 s
3.43 dd (4.5, 11.5) _ 2.31 dddd (2.5, 12.5) 4.15 s 5.05 s 4.95 s 0.71 s 4.76 s 4.50 s -
4.58 s 5.06 s 5.01 s 0.73 s 5.06 s 4.68 s 2.09 s 2.05 s
Values in parentheses are coupling constants in Hz.
(50 mg) and (2:1), scoparone (10 mg). Re-chromatography (C,H,-EtOAc, 1: 1) of the fractions eluted with hexane-EtOAc (1:l) and purification by TLC (C,H,-EtOAc) afforded, in order: scopoletin (8 mg), l(l90 mg), 2 (100 mg), and 3 (90 mg) while the most polar fractions yielded p-sitosterol-/%D-glucoside (130 mg). 4a-Hydroxy-4P-methyldi~ydrocostol (I). C15Hj602. needles. mp 192-193” (hexane-EtOAc); IR ~2:‘~ cm-‘: 3575,3380,1630, 1160, 1080, 1005, 895; MS m/z (rel. int.): 238 [M]’ (2), 220 [M -H,O]+ (13), 202 [M-2H,O]+ (15), 187 [M-2H,O-Me]’ (15), 162 (41), 135 (71), 81(58), 71 (69); ‘H NMR: see Table 1; 13C NMR(CDCI,;C-1-C-15): 842.15,20.12,43.46,72.19,55.0,27.32, 41.09,26.59,44.71,34.66,154.11,65.26,107.89, 18.68,22.70(some signals may be interchangeable). Acetylation of compound 1. Compound 1 was acetylated with Ac,O-pyridine for 12 hr and usual work-up gave the acetate la: C 17H 280 3, gum; IR v:::‘~ cm-‘: 3500, 1750, 1700, 1280, 1130, 850; MS m/z (rel. mt.): 280 [M]’ (4), 262 [M -H,O]’ (6), 220 [M-HOAc]+ (15), 187(19), 177(28), 151(48),81(55),69(86). ‘H NMR: see Table 1. Oxidation ofcompound 1. Compound l(l30 mg) was dissolved in Me&O (30 ml) and cooled in ice. While the mixture was continually stirred, Jones’ reagent was added in drops to slight excess. The mixture was stirred for a further 5 min then excess reagent was removed with MeOH, the mixture was extracted and the solvent evapd to dryness. The residue was subjected to TLC (hexane-EtOAc, 1:l) to give lb (60 mg); ‘H NMR data identical to those given in ref. [l]. Treatment of lb with excess jones’ reagent for 4 hr at room temp. afforded lc (40 mg); ‘H NMR data identical to those in the lit. [2]. Methylabion of compound lc. Compound lc (40 mg) was dissolved in Et,0 and CH,N, was added to give Id (30 mg); ‘H NMR data identical to those given in ref. [2]. lb-Hydroxycostol (2). C 15H 240 a, needles, mp 149-150 (hex_EtOAc). IR ~2:” cm-‘: 3560,3360, 1630, 1430,880, SSO, MS m/z (rel. int.): 236 [M]’ (4), 218 [M-H,O]+ (17), 200 [M -2H,O]+ (15), 185 [M-2H,O-Me]+ (18), 159 (40), 107 (46), 95 (48), 91 (73); ‘H NMR: see Table 1. Acetylation of compound 2. Compound 2 (20 mg) was acetylated as described for 1, giving 2a (25 mg) as an oil, C,,HZsO,; IR
VCHcl, ntax
cm-‘: no hydroxy band, 1720,1630,1425,1240,1015,885, MS m/z (rel. int.): 320 [M]’ (l), 260 [M-HOAc]’ (17), 200 [M -2HOAcl” (lOO), 185 [M-2HOAc-Me]’ (81), 157 (58), 91 (59); ‘H NMR: see Table 1. Oxidation ofcompound 2. Compound 2 (50 mg) was oxidized as described for 1, giving 2b (25 mg). Treatment of 2b with CHzCl, m Et,0 gave 2c (20 mg); ‘H NMR data identical to those already reported [4]. 3a-Hydroxycostol(3). C15HZ402, gum; IR ~2:‘~ cm-‘: 3560, 3380, 1630, 1440, 1360, 1130, 1080, 890, MS m/z (rel. int.): 236 [M]‘(7),218[M-H,0]+(10),203[M-H,O-Me]+(10),133 (33), 107 (40), 91 (49), 60 (88); ‘H NMR: see Table 1. Acetylation 0s compound 3. Acetylation of 3 (30 mg) in A@-pyridine for 24 hr and usual work-up gave the acetate 3a: Cl,H,,O,, gum; IR v%:‘~ cm-‘: 1720, 1630, 1360, 1240, 1020, 910, 890, MS m/z (rel. int.): 320 [M]’ missing 260 [M -HOAc]+ (7), 200 [M-2HOAc]+ (17), 185 [M-2HOAc -Me]+ (17), 177 (43), 171 (47), 117 (67), 98 (90); ‘H NMR: see Table 1. Acknowledgements-This work has been partly financed by a grant from CICYT (PB88-0049). AGG is indebted to the AIETI Foundation, Madrid.
REFERENCES 1. Bohhnann, F., Ates, N. and Jakupovic, J. (1983) Phybochemistry 22, 1159. 2. Sanz., J. F., Castellano, G. and Marco, J. A. (1990) Phytochemistry 29, 541. 3. Bohhnann, F., Jakupovic, J., King, R. M. and Robinson, H. (1981) Pkytochemistry 20, 1613. 4. Van Hijfte, L. and Vandewalle, M. (1982) Tetrahedron Letters X3,2229. 5. Herz,, W., Subramanian, P. S. and Gelssman, T. A. (1968) J. Org. Chem. 10, 3743. 6. Ahmed, A. A. and Jakupovic, J. (1990) Phytochemistry 29, 3658.