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Two New Butenolide Derivatives from Erigeron acer1
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CHEM. RES. CHINESE U. 2006, 22( 1 ) , 33-35
Two New Butenolide Derivatives from Erigeron acer * WU Gang, FEI Dong-qing and GAO Kun * * State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Larwrhou University, Lanzhou 730000, P. R. China Received July 14, 2005 Two new butenolide derivatives, named as erigeracerin A and erigeracerin B , which are a pair of epimers , were isolated from Erigeron arer. Their structures were elucidated by spectroscopic analysis including 2D NMR and
HR-ESI-MS. Keywords Erigeron acer ; Compositae ; Erigeracerin ; Butenolide derivatives Article ID 1005-9040(2006) -01 -033-03
Introduction The genus Erigeron ( Compositae ) is widely distributed in Asia, North America and Europe. There are about 35 species distributed in China, some of which have a long history of application in Chinese folk medicine"]. Sesquiterpenes have been reported as the main constituents in the genus by a Japanese research 2' besides diterpene14' and group' and our group acetylenic compound^'^ . In the course of our continuing the research on this genus, we investigated Erigeron acer, which is used to relieve toothache and arthralgiaI6]. Herein we report the isolation and the structure determination of erigeracerin A ( compound 1 ) and erigeracerin B ( compound 2 ) ( Scheme 1 ) obtained from the acetone extract of this species.
trometer. The UV spectra were obtained on a Tu-1901 UV-Vis spectrometer. The CD spectra were recorded on a JASCO J-20C Recording spectropolarimeter. The NMR spectra were recorded on a Varian MercuryH NMR spectra at 300BB NMR instrument ( t h e
'
300 MHz and the I3C NMR spectra at 75 MHz) with TMS as the internal standard and CDC1, as the solvent. The EI-MS spectra were measured on a VG ZAB-HS MS instrument at 70 eV and the positive HR-ESI-MS was carried out on a Bruker APEX II with glycerol as the matrix. Silica gel ( 200-300 mesh ) used for column chromatography ( CC ) and silica GF,, ( 1040 p ) for thin-layer chromatography ( TLC ) were supplied by the Qingdao Marine Chemical Factory, Qingdao, P. R. China. The TL chromatograms were detected at 254 nm by heating after being sprayed with 5 %
H,SO, in C,H,OH ( volume fraction). Plant Material The whole plant Erigeron acer was collected in
2 0
1 Erigeracerin A(4R, 2 Erigeracerin B(4R,
7s or 7 R ) 7s or 7 R )
Scheme 1 The structures of compounds 1 and 2.
Experimental 1 Instruments The optical rotations were measured by using a Perkin Elmer polarimeter( Model 341 ) . The IR spectra were obtained on a Nicolet NEXUS 670 FT-IR spec-
Zhangxian district, Gansu Province, China and authenticated by Professor Zhang G. L. , School of Life Sciences, Lanzhou University, where a voucher specimen has been deposited.
3 Extraction and Isolation The dried and powdered whole plant of Erigeron acer( 5.5 kg) was extracted 3 times ( 7 d each time) with acetone at room temperature. The combined extracts were evaporated to dryness ( 172.5 g ) under reduced pressure. Then the residue was separated by
* Supported by the National Natural Science Foundation of China( Nos. 20021001 and 20372029) and by the Key Project of Chinese Ministry of Education( No. 104178). * * To whom correspondence should addressed. E-mail: npchem@ lzu. edu. cn
CHEM. RES. CHINESE U.
34
column chromatography over 1800 g silica gel ( 200300 mesh) eluted with a gradient of petroleum etheracetone( 1: 0-4: 1 , volume ratio) to give 6 crude fractions( Fr. 1 , Fr. 2 , Fr. 3 and Fr. 4 , Fr. 5 and Fr. 6 ) based on the TLC test. Fr. 4 was chromatographed on a silica gel column eluted with a gradient of chloroformacetone( 50: 1-4: 1 , volume ratio) to give four subfractions: Fr. 4-1, Fr. 4-2, Fr. 4-3, Fr. 4-4. Fr. 4-1 was chromatographed on a silica gel column eluted with CHC1,-EtOAc( 10: 1 , volume ratio), and then chromatographed by PTLC over a silica gel plate by using chloroform-acetone( 10: 1 , volume ratio) as a developing system to give compound 2 ( 9 mg) . Fr. 4-3 was chromatographed on a silica gel column eluted with a Table 1
VOl. 22
gradient of CHC1,-EtOAc( 10: 1 - 4 :
1 , volume ratio)
to give two fractions: Fr. 4-3-1 and Fr. 4-3-2. Fr. 4-3-1 was chromatographed on a silica gel column eluted with
CHC1,-EtOAc( 10: 1 , volume ratio) , and then chromatographed by FTLC over a silica gel plate by using chloroform-acetone( 10: 1 , volume ratio) as a developing system to give compound 1 ( 13 mg) . Compound 1 , erigeracerin A, a yellow oil, 20 [ a ] = - 8"( c 0. 70, CH,OH) . IR( KBr) , 6/cm - I : 1759, 1713, 1663 ; UV, A,, ( CH, OH)/nm ( lgs) : 222 ( 2.64 ) , 267 ( 0.35 ) , 283 ( 0. 35 ) ; ' H and 13C NMR data see Table 1 ; EI-MS, m/z: 224, 182 ( M-CH,CO) ; HR-ESI-MS, m / t : 247.0946, calc. for C,,H,,O,Na: 247.0941.
'H NMR(300 MHz) and I3C NMR(75 MHz) data of compounds 1 and 2( CDCI, , 6 ) ~~~~~~~
NO.
Compound 2
Compound 1
8"
8"
6C
8C
-
172.4 129.8 150.9 85. 3 10. 6 22.4
172.6 130. 1 150.8 84. 6
-
1 2
-
3 4
6.95(q, 1 . 8 )
7.04( q , 1.2)
-
-
5
1.89(d, 1 . 8 ) 1.41 ( s )
1.92(d, 1.2) 1.42( s )
3.35(dd, 2 . 9 , 11.1) 3.06( dd, 11. 1, 18.2)
3.46(dd, 3 , 11.1) 2.76( dd, 11. 1, 18.2) 2.45(dd, 3 , 18.2)
6 7 8
2.73(dd, 2.9, 18.2) 9 10 11 12
Compound 2
Compound 1
2. 13( s)
-
2.08( s)
-
-
2.42( s )
2.31 ( s )
Compound 2 , erigeracerin B , a yellow oil, [a!]:= + 4 " ( c 1 . 0 0 , CH,OH). IR(KBr), 6 / c m - ' : 1760, 1712, 1663; UV, A,, (CH,OH)/nm( 1gE) : 222( 2.65 ) , 267 ( 0 . 3 5 ) , 283 ( 0 . 3 5 ) ; ' H and 13C NMR: see Table 1 ; EI-MS, m / z : 224, 182 ( M-CH,CO ) ; HR-ESI-MS , m / z : 247.0949, calc. for C12Hl,0,Na: 247.0941.
Results and Discussion 20
Compoundl, [ a I D= - 8 " ( c 0 . 7 0 , CH,OH), was obtained as a yellow oil. The molecular formula of compound 1 was determined to be C,, HI, 0, by HR-ESI-MS( m/z 247.0946, calc. for C,, H,, 0, Na: 247.0941 ) . The IR spectrum shows a strong absorption band of the ketone carbonyl group ( 1759 cm ) . The UV spectral data( CH,OH) at A,,= 267 and A,,,= 283 nm and the l3 C NMR data at 6 = 205.7 ( C ) and 6 = 207.9 ( C) suggest the presence of two ketone carbony1 groups. Furthermore, the IR absorption peaks at 1713 and 1663 c m - ' indicate that there is a structure unit of a , P-unsaturated y-lactone in compound 1 , which is supported by the I3C NMR and DEPT spectral
10. 6
53. 9 42. 8
23. 3 53.2 42. 7
205.7
205.9
29. 6 207.9
29. 5 209.0
32. 1
33. 1
data at 6 = 172.4( C) , 150.9( CH) and 129.8( C ) . By comparing the spectral data of compound 1 with those of the known compound 2,4-dimethyl4hydroxymethyl-2-b~tenolide[~' , we can see that compound 1 has a butenolide skeleton. A further detail analysis of the H NMR , I3C NMR and DEPT spectral data indicate that compound 1 has four methyl groups, one methylene group, two methine groups, and five quaternary carbon atoms. The framework of the molecule and the positions of the functional groups were further determined by the 2D NMR experiments. In the spin 'H-'H COSY spectrum, only a -CH2-CHsystem is present; as shown in Scheme 2 , HMBC correlations are observed for H7 (6, = 3. 35 ) , H12 (6, = 2.31)/C11(6, = 2 0 7 . 9 ) ; H8(6, ~ 3 . 0 6 2, . 7 3 ) , HlO(6, =2.13)/C9(6, ~ 2 0 5 . 7 ) ;H3(6, = 6 . 9 5 ) , H6(6, = l . 4 1 ) and H7(6, =3.35)/C4(SC = 8 5 . 3 ) ; H5(6, = 1 . 8 9 ) and H3(6, =6.95)/C1(SC =172.4) and C2 ( 6 , = 129.8) ; H6(6, = l . 4 1 )/C7 (6, = 5 3 . 9 ) ; H7 ( 6 , = 3 . 3 5 ) / c 3 (6, = 150.9) ; H8 (6, = 3.06, 2.73)/C4(6, = 8 5 . 3 ) .
No. 1
WU Gang et al.
35
HR-ESI-MS [ m/z 247.0949, calc. for C,, H,, 0, Na :
0
Scheme 2
-
HMRC 'H-'H COSY
The important HMBC( H to C ) correlations of compounds 1 and 2.
Thus the planar structure of compound 1 was determined. Compound 1 has two chiral carbon atoms, C4 and C7. The absolute configuration of C7 is difficult to determine, but the absolute configuration of C4 can be deduced by the CD spectrum. A negative Cotton effect at 234 nm ( A&: - 0. 14 ) attributed to the unsaturated y-lactone is observed for compound 1. Application of the lactone sector ruleL8' and the building of the molecular model of compound 1 indicate that the absolute configuration of C4 is R. Consequently, compound 1 was identified as( 4 R , 7S/7R) -2,4-dimethyl4-( 1 '-acetyl-3'-oxobutyl) -2-butenolide. It may be derived biogenetically from butenolides which occur widely in the nature"'. Compound2, [a]'," = + 4 " ( c 1.00, CH,OH), was obtained as a yellow oil. The molecular formula of compound 2 was also determined to be CI2 H,, 0, by
247.0941 1. The IR, UV, ' H and 13C NMR spectral data of compound 2 are similar to those of compound 1 (Table 1 ) . The proton and carbon signals were assigned by a detailed comparison of the NMR spectral data of compound 2 with those of compound 1 and by 2D-NMR experiments of compound 2. Interestingly, the HMBC correlations indicate that the planar structure of compound 2 is identical to that of compound 1. Therefore, compounds 2 and 1 must be a pair of isomers. A negative Cotton effect at 231 nm ( A& = - 0. 17 ) '81 indicates that the absolute configuration at C4 of compound 2 is also R. Thus, compound 2 is an epimeric isomer of compound 1 at C7.
References [ I ] [2 ]
[3] [4 j [5 j [6
1
[7] [8 ] 9j
Wu Z. Y. , Outline of New China Herbals. Shanghai Science and Technology Press, Shanghai, 1990, 417 Iijima T. , Yaoita Y. , Kikuchi M. , Chem. Pharrn. Bull. , 2003, 5 1 , 545 Li X. , Yang M. , Han Y. F. , Planta Medica, 2005, 7 1 , 268 Waddell T. 6. , Osborne C. B. , Collison R. , et a1 , J. Urg. Chem. , 1983, 4 8 , 4450 Jakupovic J. , Chau-Thi T. N. , Fischer N. H . , PhytochemistT, 1986, 2 5 , 1223 Pieroni A . , Quave C. L. , Santoro R. F. , J. Ethnophnrmacology , 2004, 95, 373
Still I. w'.J. , Drewery M. J. , J. Org. Chern. , 1989, 54, 290 Kagan H. B. , Stereochemistry 1I-Fundamental and Methods: Diple Moments, CD or ORD, Georg Thieme. Pub. , 1977, 33 Larock K. C. , Riefling B. , Fellows C. A. , J. Org. Chern. , 1978.43, 131
CHEM. RES. CHINESE U. 2006, 22( 1 ) , 33-35
Two New Butenolide Derivatives from Erigeron acer * WU Gang, FEI Dong-qing and GAO Kun * * State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Larwrhou University, Lanzhou 730000, P. R. China Received July 14, 2005 Two new butenolide derivatives, named as erigeracerin A and erigeracerin B , which are a pair of epimers , were isolated from Erigeron arer. Their structures were elucidated by spectroscopic analysis including 2D NMR and
HR-ESI-MS. Keywords Erigeron acer ; Compositae ; Erigeracerin ; Butenolide derivatives Article ID 1005-9040(2006) -01 -033-03
Introduction The genus Erigeron ( Compositae ) is widely distributed in Asia, North America and Europe. There are about 35 species distributed in China, some of which have a long history of application in Chinese folk medicine"]. Sesquiterpenes have been reported as the main constituents in the genus by a Japanese research 2' besides diterpene14' and group' and our group acetylenic compound^'^ . In the course of our continuing the research on this genus, we investigated Erigeron acer, which is used to relieve toothache and arthralgiaI6]. Herein we report the isolation and the structure determination of erigeracerin A ( compound 1 ) and erigeracerin B ( compound 2 ) ( Scheme 1 ) obtained from the acetone extract of this species.
trometer. The UV spectra were obtained on a Tu-1901 UV-Vis spectrometer. The CD spectra were recorded on a JASCO J-20C Recording spectropolarimeter. The NMR spectra were recorded on a Varian MercuryH NMR spectra at 300BB NMR instrument ( t h e
'
300 MHz and the I3C NMR spectra at 75 MHz) with TMS as the internal standard and CDC1, as the solvent. The EI-MS spectra were measured on a VG ZAB-HS MS instrument at 70 eV and the positive HR-ESI-MS was carried out on a Bruker APEX II with glycerol as the matrix. Silica gel ( 200-300 mesh ) used for column chromatography ( CC ) and silica GF,, ( 1040 p ) for thin-layer chromatography ( TLC ) were supplied by the Qingdao Marine Chemical Factory, Qingdao, P. R. China. The TL chromatograms were detected at 254 nm by heating after being sprayed with 5 %
H,SO, in C,H,OH ( volume fraction). Plant Material The whole plant Erigeron acer was collected in
2 0
1 Erigeracerin A(4R, 2 Erigeracerin B(4R,
7s or 7 R ) 7s or 7 R )
Scheme 1 The structures of compounds 1 and 2.
Experimental 1 Instruments The optical rotations were measured by using a Perkin Elmer polarimeter( Model 341 ) . The IR spectra were obtained on a Nicolet NEXUS 670 FT-IR spec-
Zhangxian district, Gansu Province, China and authenticated by Professor Zhang G. L. , School of Life Sciences, Lanzhou University, where a voucher specimen has been deposited.
3 Extraction and Isolation The dried and powdered whole plant of Erigeron acer( 5.5 kg) was extracted 3 times ( 7 d each time) with acetone at room temperature. The combined extracts were evaporated to dryness ( 172.5 g ) under reduced pressure. Then the residue was separated by
* Supported by the National Natural Science Foundation of China( Nos. 20021001 and 20372029) and by the Key Project of Chinese Ministry of Education( No. 104178). * * To whom correspondence should addressed. E-mail: npchem@ lzu. edu. cn
CHEM. RES. CHINESE U.
34
column chromatography over 1800 g silica gel ( 200300 mesh) eluted with a gradient of petroleum etheracetone( 1: 0-4: 1 , volume ratio) to give 6 crude fractions( Fr. 1 , Fr. 2 , Fr. 3 and Fr. 4 , Fr. 5 and Fr. 6 ) based on the TLC test. Fr. 4 was chromatographed on a silica gel column eluted with a gradient of chloroformacetone( 50: 1-4: 1 , volume ratio) to give four subfractions: Fr. 4-1, Fr. 4-2, Fr. 4-3, Fr. 4-4. Fr. 4-1 was chromatographed on a silica gel column eluted with CHC1,-EtOAc( 10: 1 , volume ratio), and then chromatographed by PTLC over a silica gel plate by using chloroform-acetone( 10: 1 , volume ratio) as a developing system to give compound 2 ( 9 mg) . Fr. 4-3 was chromatographed on a silica gel column eluted with a Table 1
VOl. 22
gradient of CHC1,-EtOAc( 10: 1 - 4 :
1 , volume ratio)
to give two fractions: Fr. 4-3-1 and Fr. 4-3-2. Fr. 4-3-1 was chromatographed on a silica gel column eluted with
CHC1,-EtOAc( 10: 1 , volume ratio) , and then chromatographed by FTLC over a silica gel plate by using chloroform-acetone( 10: 1 , volume ratio) as a developing system to give compound 1 ( 13 mg) . Compound 1 , erigeracerin A, a yellow oil, 20 [ a ] = - 8"( c 0. 70, CH,OH) . IR( KBr) , 6/cm - I : 1759, 1713, 1663 ; UV, A,, ( CH, OH)/nm ( lgs) : 222 ( 2.64 ) , 267 ( 0.35 ) , 283 ( 0. 35 ) ; ' H and 13C NMR data see Table 1 ; EI-MS, m/z: 224, 182 ( M-CH,CO) ; HR-ESI-MS, m / t : 247.0946, calc. for C,,H,,O,Na: 247.0941.
'H NMR(300 MHz) and I3C NMR(75 MHz) data of compounds 1 and 2( CDCI, , 6 ) ~~~~~~~
NO.
Compound 2
Compound 1
8"
8"
6C
8C
-
172.4 129.8 150.9 85. 3 10. 6 22.4
172.6 130. 1 150.8 84. 6
-
1 2
-
3 4
6.95(q, 1 . 8 )
7.04( q , 1.2)
-
-
5
1.89(d, 1 . 8 ) 1.41 ( s )
1.92(d, 1.2) 1.42( s )
3.35(dd, 2 . 9 , 11.1) 3.06( dd, 11. 1, 18.2)
3.46(dd, 3 , 11.1) 2.76( dd, 11. 1, 18.2) 2.45(dd, 3 , 18.2)
6 7 8
2.73(dd, 2.9, 18.2) 9 10 11 12
Compound 2
Compound 1
2. 13( s)
-
2.08( s)
-
-
2.42( s )
2.31 ( s )
Compound 2 , erigeracerin B , a yellow oil, [a!]:= + 4 " ( c 1 . 0 0 , CH,OH). IR(KBr), 6 / c m - ' : 1760, 1712, 1663; UV, A,, (CH,OH)/nm( 1gE) : 222( 2.65 ) , 267 ( 0 . 3 5 ) , 283 ( 0 . 3 5 ) ; ' H and 13C NMR: see Table 1 ; EI-MS, m / z : 224, 182 ( M-CH,CO ) ; HR-ESI-MS , m / z : 247.0949, calc. for C12Hl,0,Na: 247.0941.
Results and Discussion 20
Compoundl, [ a I D= - 8 " ( c 0 . 7 0 , CH,OH), was obtained as a yellow oil. The molecular formula of compound 1 was determined to be C,, HI, 0, by HR-ESI-MS( m/z 247.0946, calc. for C,, H,, 0, Na: 247.0941 ) . The IR spectrum shows a strong absorption band of the ketone carbonyl group ( 1759 cm ) . The UV spectral data( CH,OH) at A,,= 267 and A,,,= 283 nm and the l3 C NMR data at 6 = 205.7 ( C ) and 6 = 207.9 ( C) suggest the presence of two ketone carbony1 groups. Furthermore, the IR absorption peaks at 1713 and 1663 c m - ' indicate that there is a structure unit of a , P-unsaturated y-lactone in compound 1 , which is supported by the I3C NMR and DEPT spectral
10. 6
53. 9 42. 8
23. 3 53.2 42. 7
205.7
205.9
29. 6 207.9
29. 5 209.0
32. 1
33. 1
data at 6 = 172.4( C) , 150.9( CH) and 129.8( C ) . By comparing the spectral data of compound 1 with those of the known compound 2,4-dimethyl4hydroxymethyl-2-b~tenolide[~' , we can see that compound 1 has a butenolide skeleton. A further detail analysis of the H NMR , I3C NMR and DEPT spectral data indicate that compound 1 has four methyl groups, one methylene group, two methine groups, and five quaternary carbon atoms. The framework of the molecule and the positions of the functional groups were further determined by the 2D NMR experiments. In the spin 'H-'H COSY spectrum, only a -CH2-CHsystem is present; as shown in Scheme 2 , HMBC correlations are observed for H7 (6, = 3. 35 ) , H12 (6, = 2.31)/C11(6, = 2 0 7 . 9 ) ; H8(6, ~ 3 . 0 6 2, . 7 3 ) , HlO(6, =2.13)/C9(6, ~ 2 0 5 . 7 ) ;H3(6, = 6 . 9 5 ) , H6(6, = l . 4 1 ) and H7(6, =3.35)/C4(SC = 8 5 . 3 ) ; H5(6, = 1 . 8 9 ) and H3(6, =6.95)/C1(SC =172.4) and C2 ( 6 , = 129.8) ; H6(6, = l . 4 1 )/C7 (6, = 5 3 . 9 ) ; H7 ( 6 , = 3 . 3 5 ) / c 3 (6, = 150.9) ; H8 (6, = 3.06, 2.73)/C4(6, = 8 5 . 3 ) .
No. 1
WU Gang et al.
35
HR-ESI-MS [ m/z 247.0949, calc. for C,, H,, 0, Na :
0
Scheme 2
-
HMRC 'H-'H COSY
The important HMBC( H to C ) correlations of compounds 1 and 2.
Thus the planar structure of compound 1 was determined. Compound 1 has two chiral carbon atoms, C4 and C7. The absolute configuration of C7 is difficult to determine, but the absolute configuration of C4 can be deduced by the CD spectrum. A negative Cotton effect at 234 nm ( A&: - 0. 14 ) attributed to the unsaturated y-lactone is observed for compound 1. Application of the lactone sector ruleL8' and the building of the molecular model of compound 1 indicate that the absolute configuration of C4 is R. Consequently, compound 1 was identified as( 4 R , 7S/7R) -2,4-dimethyl4-( 1 '-acetyl-3'-oxobutyl) -2-butenolide. It may be derived biogenetically from butenolides which occur widely in the nature"'. Compound2, [a]'," = + 4 " ( c 1.00, CH,OH), was obtained as a yellow oil. The molecular formula of compound 2 was also determined to be CI2 H,, 0, by
247.0941 1. The IR, UV, ' H and 13C NMR spectral data of compound 2 are similar to those of compound 1 (Table 1 ) . The proton and carbon signals were assigned by a detailed comparison of the NMR spectral data of compound 2 with those of compound 1 and by 2D-NMR experiments of compound 2. Interestingly, the HMBC correlations indicate that the planar structure of compound 2 is identical to that of compound 1. Therefore, compounds 2 and 1 must be a pair of isomers. A negative Cotton effect at 231 nm ( A& = - 0. 17 ) '81 indicates that the absolute configuration at C4 of compound 2 is also R. Thus, compound 2 is an epimeric isomer of compound 1 at C7.
References [ I ] [2 ]
[3] [4 j [5 j [6
1
[7] [8 ] 9j
Wu Z. Y. , Outline of New China Herbals. Shanghai Science and Technology Press, Shanghai, 1990, 417 Iijima T. , Yaoita Y. , Kikuchi M. , Chem. Pharrn. Bull. , 2003, 5 1 , 545 Li X. , Yang M. , Han Y. F. , Planta Medica, 2005, 7 1 , 268 Waddell T. 6. , Osborne C. B. , Collison R. , et a1 , J. Urg. Chem. , 1983, 4 8 , 4450 Jakupovic J. , Chau-Thi T. N. , Fischer N. H . , PhytochemistT, 1986, 2 5 , 1223 Pieroni A . , Quave C. L. , Santoro R. F. , J. Ethnophnrmacology , 2004, 95, 373
Still I. w'.J. , Drewery M. J. , J. Org. Chern. , 1989, 54, 290 Kagan H. B. , Stereochemistry 1I-Fundamental and Methods: Diple Moments, CD or ORD, Georg Thieme. Pub. , 1977, 33 Larock K. C. , Riefling B. , Fellows C. A. , J. Org. Chern. , 1978.43, 131