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4,5-seco-african-4,5-dione from lippia integrifolia
Phytochemistry,Vol. 31, No. 11, pp. 40254026, 1992 Printed in Great Britain.
0
003 I -9422/92 $5.00 + 0.00 1992 Pergamon Press Ltd
SHORT REPORTS 4,5-SECO-AFRICAN-4,5-DIONE
FROM LIPPIA INTEGRIFOLIA
CESAR A. N. CATALAN,* INES J. S. DE FENIK, PATRICIA J. DE ARRIAZU
and W. C. M. C. KOKKE~
Instituto de Quimica Orglnica, Facultad de Bioquimica, Quimica y Farmacia, Universidad National de TucumPn, Ayacucho 491, S. M. de Tucumitn 4000, Argentina; tCollege of Business and Administration, Graduate MBA, St. Joseph’sUniversity, Philadelphia,
PA 19131,U.S.A. (Received in revisedform17 February 1992) Key Word Index-Lippia
integri@ia; Verbenaceae; sesquiterpenoids; 4,5-seco-african-4,5-dione; essential oil.
Abstract-The polar fractions of the essential oil from Lippia integrijblia yielded the first sesquiterpene based on the 4,5-seco-africane skeleton. The structure was elucidated by spectroscopic methods.
Lippia integr$olia (Griseb.) Hieron. commonly known as ‘incayuyo’ or ‘poleo’ is a woody aromatic shrub native to central and northern Argentine where the aerial parts are used in traditional medicine [l] as a diuretic, emmenagogue, stomachic and nervine. Previous studies [24] showed that the essential oil is a rich source of sesquiterpenoids with novel carbon skeletons. We report here the isolation of the first 4,5-seco-africane derivative from the more polar fractions of the volatile oil of L. integrifolia. The rare africane skeleton was first found [5] in africanol (l), a tertiary alcohol isolated from a marine invertebrate. A second representative was isolated four years later from the shrub Senecio oxyriijblius [6], but in this paper the skeleton was named senoxyriane by the authors who overlooked ref. [S]. Diketone 2 eluted after spathulenol and integrifolianl$dione [2] by CC on silica gel. It was isolated as an oil which on mass spectral analysis showed m/z 236.177 [M]’ in accord with the molecular formula C,,H,,O,. The IR spectrum displayed diagnostic absorptions at 3050,1703 and 1024 cm- ‘. The 13C NMR data revealed two carbonyl groups (6208.8 and 209.3), four methyls, two quaternary carbons, two methines and five methylenes. These data together with the absence of vinyl protons in the ‘H NMR spectrum and olefinic carbons in the 13CNMR spectrum indicate a bicyclosesquiterpene diketone. A doublet of doublets at 60.30 in the ‘H NMR spectrum (CDCl,) coupled to a doublet of doublets at 60.74 and to a four-fold doublet at 60.66 along with the IR absorptions at 3050 and 1024 cm-’ indicate a 1,1,2trisubstituted cyclopropane, as the two first signals show a couplig of J =4.2 Hz with each other, typical for a geminal coupling of cyclopropyl protons [7]. The proton resonating at 60.66 is further coupIed to the protons of a methylene group that appear at 6 1.34 dd, and 62.01 ddd. Further, the presence of a doublet at 62.18 coupled to a doublet of doublets at 62.25 indicates the fragment -CO-CH,which is connected through a quaternary carbon with the methylene group attached to the cyclopropane because the signal at 62.25 shows a W-coupling
*Author to whom correspondence should he addressed.
.%,,, CD ;’
H -_
“,
OH
1
2
of 1.7 Hz with the proton resonating at 62.01. Extensive DR experiments and a ‘H-‘H 2D COSY spectrum also established the presence of the fragment MeCOCH,CH,CH which is connected to a carbonyl and a quaternary carbon. Accommodation of the remaining three methyls singlet is straightforward. Both the ‘H and 13CNMR data (see Table 1 and Experimental) are in agreement with structure 2. The relative stereochemistry was deduced by NOE difference spectrometry. Clear effects were observed between H-lla, H-l (8%) and H-8 (7%), between H-l, H-8 (10%) and H-lla (7%) as well as between H-14, H-9 (4%) and H-llfi (3.5%) while no effect between H-14 and H-l was obtained. Most likely an africane derivative with oxygen functions at C-4 and C-5 is a precursor of 2.
4025
Short Reports Table 1. ‘H NMR spectral data of compound 2 (400 MHz)* H
CM313
C6D6
DMSO-d,
1 2 2 3 3’ 6a 68
2.19 dd 1.81 dddd 2.01 dddd 2.36 ddd 2.44 ddd 2.18 d 2.25 dd 1.34 dd 2.01 ddd 0.66 dddd 0.30 dd 0.74 dd
1.98 m* 1.82 m* 2.10 m* 2.05 m* 1.97 m* 1.88
2.22 1.60 1.74 2.32 2.36 2.26
2.20
2.06
1.01 1.68
1.41 1.89
0.38
0.59
0.11 0.51
0.33
8a
88 9P lla 11s
12 w
0.97 s
14t
0.87 s
15t
2.13 s
1.00s
0.86 0.73
0.81 1.65
0.68 0.87 0.76 0.94
2.06
*Unless noted otherwise multiplicities in C,D, and DMSO-d, are the same as in CDCl,. tlntensity three protons, $,Not first order. J (Hz) (in CDCI,) 1,2=6.5; 1,2’=7.5; 2,2’= 14; 2,3 =6.3; 2,3’= 7.8; 2’,3= 7.7; 2’,3’= 7.2; 3,3’= 17; 6x,68=11.4; 6B,SjI=l.7; 8a,8B=l4.8; 8a,9=11; 8/?,9=6; 9,lla=4.2; 9,11/?=8.5; llqll/I=4.2.
EXPERIMRNTAL
Air-dried aerial parts of L. integrifolia were purchased from a local market. Isolation ofcompound 2. The essential oil (63 g) was obtained by steam-distillation from 9.6 kg of aerial parts (mainly Ieaves) and subjected to fractional vacuum distillation through a short
column to give 4 frs: I, 2.33 g, bp 32-38” (4 mm); II, 2.01 g, bp 3847” (3.5 mm); III, 4.93 g, bp 45-67 (2.5 mm); IV, 21.3 g, bp 67-94” (2.5 mm) and a residue of 28.1 g. A portion of the residue (26.3 g) was subjected to CC on silica gel using hexane with increasing amounts of Et,0 (24O%k 75 frs were collected and monitored by TLC. Frs 2429 consisted mainly of spathulenol with minor amounts of integrifolian-1,5-dione [S]. Frs 4@42 which eluted with hexane-Et,0 (17 : 3) were combined (125 mg) and a portion (60mg) processed by HPLC (C8 column, MeOH-Ha0 2: 1) to give 33 mg of 2. 4,5-sect-African-4,5-dione (2). Oil. IR vg: cn-‘: 3050, 1703, 1403, 1385, 1368, 1283, 1164, 1024. ‘HNMR: see Table 1. ‘sCNMR (100 MHz, CDCl,): 6209.3 (C-5), 208.8 (C-4), 60.3 (C6), 53.6 (C-l), 42.5 (C-3), 41.4 (C-8), 35.2 (C-7), 32.4 (C-13), 29.8 (C12),25.2(C-15),23.5(C-2),21.8(C-9),21.3 (C-11), 19.1(C-14), 16.8 (C-10). EIMS m/e (rel. int.): 236.177 [M]’ (21) (Calc. for C,,H,,O,: 236.177), 218 (23), 203 (ll), 193 (5), 179 (25), 161 (27), 125 (42), 112 (lOOk 9.5 (35). 81 (33), 43 (68). CIMS (gas reagent CH,): m/z (rel. int.): 237 ([M+ l]‘, lOO),219 (60), 201 (14), 195 (4.7). 179 (22), 177 (14.6) 161 (35.5) 125 (17) 112 (lS), 99 (75), 85 (14). Acknowledgement-Work in Tucuman was supported by grants from the Consejo National de Investigaciones Cientificas y T&micas de la Republica Argentina y Fundacion Antorchas. REFERENCES
1. Toursarkissian, M. (1980) PlantasMedicinales de la Argentina, p. 135. Editorial Hemisferio Sur, Buenos Aires. Catalan, C. A. N., Socolsky de Fenik, I. J. S., Dartayet, G. H. and Gras, E. G. (1991) Phytochemistry 30, 1323. 3. Catalan, C. A. N., Acoata de Iglesias, D. I., Retamar, J. A., Iturraspe, J. B., Dartayet, G. H. and Gros, E. G. (1983) Phytochemktry 22, 1507. 4. Dartayet, G. H., Catalan, C. A., Retamar, J. A and Gros, E. G. (1984) Phytochemistry 23, 688. 5. Tursch, B., Brackmann, J. C., Daloze, D., Fritz, P., Kelecom, A., Karlsson, R. and Losman, D. (1974) Tetrahedron Letters 747.
6. Bohlmann, F. and Zdero, C. (1978) Phytochemistry 17, 1669. 7. Pated, D. J., Honden, M. E. H. and Roberts, J. D. (1963)J. Am. Chem. Sot. 85, 3218.
0
003 I -9422/92 $5.00 + 0.00 1992 Pergamon Press Ltd
SHORT REPORTS 4,5-SECO-AFRICAN-4,5-DIONE
FROM LIPPIA INTEGRIFOLIA
CESAR A. N. CATALAN,* INES J. S. DE FENIK, PATRICIA J. DE ARRIAZU
and W. C. M. C. KOKKE~
Instituto de Quimica Orglnica, Facultad de Bioquimica, Quimica y Farmacia, Universidad National de TucumPn, Ayacucho 491, S. M. de Tucumitn 4000, Argentina; tCollege of Business and Administration, Graduate MBA, St. Joseph’sUniversity, Philadelphia,
PA 19131,U.S.A. (Received in revisedform17 February 1992) Key Word Index-Lippia
integri@ia; Verbenaceae; sesquiterpenoids; 4,5-seco-african-4,5-dione; essential oil.
Abstract-The polar fractions of the essential oil from Lippia integrijblia yielded the first sesquiterpene based on the 4,5-seco-africane skeleton. The structure was elucidated by spectroscopic methods.
Lippia integr$olia (Griseb.) Hieron. commonly known as ‘incayuyo’ or ‘poleo’ is a woody aromatic shrub native to central and northern Argentine where the aerial parts are used in traditional medicine [l] as a diuretic, emmenagogue, stomachic and nervine. Previous studies [24] showed that the essential oil is a rich source of sesquiterpenoids with novel carbon skeletons. We report here the isolation of the first 4,5-seco-africane derivative from the more polar fractions of the volatile oil of L. integrifolia. The rare africane skeleton was first found [5] in africanol (l), a tertiary alcohol isolated from a marine invertebrate. A second representative was isolated four years later from the shrub Senecio oxyriijblius [6], but in this paper the skeleton was named senoxyriane by the authors who overlooked ref. [S]. Diketone 2 eluted after spathulenol and integrifolianl$dione [2] by CC on silica gel. It was isolated as an oil which on mass spectral analysis showed m/z 236.177 [M]’ in accord with the molecular formula C,,H,,O,. The IR spectrum displayed diagnostic absorptions at 3050,1703 and 1024 cm- ‘. The 13C NMR data revealed two carbonyl groups (6208.8 and 209.3), four methyls, two quaternary carbons, two methines and five methylenes. These data together with the absence of vinyl protons in the ‘H NMR spectrum and olefinic carbons in the 13CNMR spectrum indicate a bicyclosesquiterpene diketone. A doublet of doublets at 60.30 in the ‘H NMR spectrum (CDCl,) coupled to a doublet of doublets at 60.74 and to a four-fold doublet at 60.66 along with the IR absorptions at 3050 and 1024 cm-’ indicate a 1,1,2trisubstituted cyclopropane, as the two first signals show a couplig of J =4.2 Hz with each other, typical for a geminal coupling of cyclopropyl protons [7]. The proton resonating at 60.66 is further coupIed to the protons of a methylene group that appear at 6 1.34 dd, and 62.01 ddd. Further, the presence of a doublet at 62.18 coupled to a doublet of doublets at 62.25 indicates the fragment -CO-CH,which is connected through a quaternary carbon with the methylene group attached to the cyclopropane because the signal at 62.25 shows a W-coupling
*Author to whom correspondence should he addressed.
.%,,, CD ;’
H -_
“,
OH
1
2
of 1.7 Hz with the proton resonating at 62.01. Extensive DR experiments and a ‘H-‘H 2D COSY spectrum also established the presence of the fragment MeCOCH,CH,CH which is connected to a carbonyl and a quaternary carbon. Accommodation of the remaining three methyls singlet is straightforward. Both the ‘H and 13CNMR data (see Table 1 and Experimental) are in agreement with structure 2. The relative stereochemistry was deduced by NOE difference spectrometry. Clear effects were observed between H-lla, H-l (8%) and H-8 (7%), between H-l, H-8 (10%) and H-lla (7%) as well as between H-14, H-9 (4%) and H-llfi (3.5%) while no effect between H-14 and H-l was obtained. Most likely an africane derivative with oxygen functions at C-4 and C-5 is a precursor of 2.
4025
Short Reports Table 1. ‘H NMR spectral data of compound 2 (400 MHz)* H
CM313
C6D6
DMSO-d,
1 2 2 3 3’ 6a 68
2.19 dd 1.81 dddd 2.01 dddd 2.36 ddd 2.44 ddd 2.18 d 2.25 dd 1.34 dd 2.01 ddd 0.66 dddd 0.30 dd 0.74 dd
1.98 m* 1.82 m* 2.10 m* 2.05 m* 1.97 m* 1.88
2.22 1.60 1.74 2.32 2.36 2.26
2.20
2.06
1.01 1.68
1.41 1.89
0.38
0.59
0.11 0.51
0.33
8a
88 9P lla 11s
12 w
0.97 s
14t
0.87 s
15t
2.13 s
1.00s
0.86 0.73
0.81 1.65
0.68 0.87 0.76 0.94
2.06
*Unless noted otherwise multiplicities in C,D, and DMSO-d, are the same as in CDCl,. tlntensity three protons, $,Not first order. J (Hz) (in CDCI,) 1,2=6.5; 1,2’=7.5; 2,2’= 14; 2,3 =6.3; 2,3’= 7.8; 2’,3= 7.7; 2’,3’= 7.2; 3,3’= 17; 6x,68=11.4; 6B,SjI=l.7; 8a,8B=l4.8; 8a,9=11; 8/?,9=6; 9,lla=4.2; 9,11/?=8.5; llqll/I=4.2.
EXPERIMRNTAL
Air-dried aerial parts of L. integrifolia were purchased from a local market. Isolation ofcompound 2. The essential oil (63 g) was obtained by steam-distillation from 9.6 kg of aerial parts (mainly Ieaves) and subjected to fractional vacuum distillation through a short
column to give 4 frs: I, 2.33 g, bp 32-38” (4 mm); II, 2.01 g, bp 3847” (3.5 mm); III, 4.93 g, bp 45-67 (2.5 mm); IV, 21.3 g, bp 67-94” (2.5 mm) and a residue of 28.1 g. A portion of the residue (26.3 g) was subjected to CC on silica gel using hexane with increasing amounts of Et,0 (24O%k 75 frs were collected and monitored by TLC. Frs 2429 consisted mainly of spathulenol with minor amounts of integrifolian-1,5-dione [S]. Frs 4@42 which eluted with hexane-Et,0 (17 : 3) were combined (125 mg) and a portion (60mg) processed by HPLC (C8 column, MeOH-Ha0 2: 1) to give 33 mg of 2. 4,5-sect-African-4,5-dione (2). Oil. IR vg: cn-‘: 3050, 1703, 1403, 1385, 1368, 1283, 1164, 1024. ‘HNMR: see Table 1. ‘sCNMR (100 MHz, CDCl,): 6209.3 (C-5), 208.8 (C-4), 60.3 (C6), 53.6 (C-l), 42.5 (C-3), 41.4 (C-8), 35.2 (C-7), 32.4 (C-13), 29.8 (C12),25.2(C-15),23.5(C-2),21.8(C-9),21.3 (C-11), 19.1(C-14), 16.8 (C-10). EIMS m/e (rel. int.): 236.177 [M]’ (21) (Calc. for C,,H,,O,: 236.177), 218 (23), 203 (ll), 193 (5), 179 (25), 161 (27), 125 (42), 112 (lOOk 9.5 (35). 81 (33), 43 (68). CIMS (gas reagent CH,): m/z (rel. int.): 237 ([M+ l]‘, lOO),219 (60), 201 (14), 195 (4.7). 179 (22), 177 (14.6) 161 (35.5) 125 (17) 112 (lS), 99 (75), 85 (14). Acknowledgement-Work in Tucuman was supported by grants from the Consejo National de Investigaciones Cientificas y T&micas de la Republica Argentina y Fundacion Antorchas. REFERENCES
1. Toursarkissian, M. (1980) PlantasMedicinales de la Argentina, p. 135. Editorial Hemisferio Sur, Buenos Aires. Catalan, C. A. N., Socolsky de Fenik, I. J. S., Dartayet, G. H. and Gras, E. G. (1991) Phytochemistry 30, 1323. 3. Catalan, C. A. N., Acoata de Iglesias, D. I., Retamar, J. A., Iturraspe, J. B., Dartayet, G. H. and Gros, E. G. (1983) Phytochemktry 22, 1507. 4. Dartayet, G. H., Catalan, C. A., Retamar, J. A and Gros, E. G. (1984) Phytochemistry 23, 688. 5. Tursch, B., Brackmann, J. C., Daloze, D., Fritz, P., Kelecom, A., Karlsson, R. and Losman, D. (1974) Tetrahedron Letters 747.
6. Bohlmann, F. and Zdero, C. (1978) Phytochemistry 17, 1669. 7. Pated, D. J., Honden, M. E. H. and Roberts, J. D. (1963)J. Am. Chem. Sot. 85, 3218.