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Diterpenoids of Conyza coulteri
Phytochemwy, Vol 27, No 4, pp 121l-1212, 1988 Prlnted III Great Brltaln
0
DITERPENOIDSOF SHIVANAND
D. JOLAD,*
BARBARA
CONYZA COULTERI
N. TIMMERMANN, FERNANDO
Uiwersity
oi?Anzona,
U S A., *Umverslty
office
ol_And~ Lands
Studies,
JOSEPH J HOFFMANN, A
ROBERT
B. BATES?
and
CAMOU?
Bloresources
Research
Facility,
Z5U E Wencla
of Arizona, College of Pharmacy, Tucson, AZ X5721, U S A, tUmverslty
Tucson,
0031 ~9422/88 9300+000 1988 Pergamoo Journals Ltd
Road; l%cson,
of Arizona, Department
AZ K57U6;
of Chemistry,
AZ 85721, U S A.
(Recewed 24 June 1987) Key Wbrdrnd~x--C’onyza acid, 2P-hydroxyhardwlckuc
C’oulteri; Asteraceae, Astereae, acid, bacchotrlcuneatm A
Solidigmmae,
Abstract-Four furanodlterpenolds, mcludmg three furanoclerodanes, parts of Conyza Coulterl One of the terpenolds, 2fl-hydroxyhardwickuc first time
INTRODUCTION
The genus Conyza IS known to produce acetylenes, diand trlterpenolds, flavones and coumarms [l-7] This note reports our examination of the chemical constltuents of Conyza Coulterl Gray, an annual herb of the southwestern United States and Mexico that IS known to be toxic to hvestock [S]. From the methylene chloride extract of C Coultert, four furanodlterpenolds (l&4), mcludmg three furanoclerodanes (2-4) were isolated and characterized mainly by spectral (NMR and MS) methods and comparisons with literature data The furanodlterpenold (1) was identified [IR i~!$“: 3000-2500 and 1690 (COOH), 1500 and 870 (furan), 3040, 1645, 1635 (C=C) cm -‘; E MS m/z. 316 (M+), 81 (furan-&HZ), 69 ()=CHE H,, base); ‘HNMR as reported] as centlpedlc acid, a constituent of Centrpeda orbuhru (Asteraceae) [9]. The three furanoclerodanes include, hardwlcknc acid (2), bacchotrlcuneatin A (3) and 2/Ghydroxyhardwicklic acid (4). Compound 2, previously reported from plants of different genera [7,10], was identified by direct comparlson with an authentic sample Compound 3, previously isolated from Baccharls trrcuneata var. trumeata [l 1, 121 and B. artrcuhta [ 131, was characterized on the basis of 0 II its spectral data [IR nail’? 1770 and 1750 (X-O-), 3015 and 1660 (C=C), 1500 and 868 (furan) 1380 (Me) cm-‘; EIMS m/z. 342 (Mf ), 312 (base), 95 (furan-CH,-eH,), 94 (furan-CH=CH,); HRMS m/z 342 1540 (+ 5.3 mmu), CZ0HZ205 and ‘H NMR as previously reported]. 2P-Hydroxyhardwlckilc acid (4) was previously prepared (1) by the saponification of 2fl+uccmyloxyhardwlckuc acid present m the acidic fraction of Dodonaea boronfoh and characterized as its methyl ester derlvatlve and (n) by synthesis, along with Its C-2 eplmer, from ent-15,16-epoxycleroda-3,13(16),14-tr~ene-2~,19-d~ol lsolated from the neutral fraction of the same species [14]. Recently, Pandey, et al. [7] reported the C-2 eplmer of 4, characterized as Its methyl ester derivative, from Conyza japonica and synthesized both eplmers from methyl hard-
diterpenoidi,
centipedic
acid; Iiard.wlcknc
have been ldentlfied m the extract of the aerial acid, was found as a natural product for the
wlckilate. Our lsolatlon of 4 is the first report of the free acid from a natural source Its spectral data [IR Lz!:13. 3600 and 1020 (OH), 3000-2500 and 1700 (COOH), 1500 and 870 (furan), 3010, 1635 and 840 (C=C) cm-‘, EIMS m/z: 332 (M+ ), 314 (M-H,O), 95 (furan-CH,-&HZ), 81 (furan&H,), ‘H NMR (6, CDCI,) 0 75 (H-20), 0 84 d (J = 5 8 Hz, H-17), 1 20 (H-19), 4.34 br s (H-2), 6.26 br s (H14), 6 63d (5=4 1 Hz, H-3), 7.20 br s (H-16), 7.31 br s (H15)] parameters are m accord with those given for Its methyl ester derivative Cl43 In particular, the signal for H-2 as a doublet (J=4 1 Hz) rather than as a doublet of doublets (J = 2.5, 1 5 Hz) defines the configuration at C-2 [7] The ‘%Z NMR parameters for 4 (see Experimental), hitherto unreported, support the structure EXPERIMENTAL Pfant material. The collectlon of C. Coulterl was made on 30 August 1985 m the Santa Rota and Huachuca mountains m Southern Arizona A voucher specimen (SPM 3039) was deposited m the Herbarium of the Umverslty of Arizona All plant material was air-dried, ground to 3 mm particle size and stored at 5” prior to extraction Extracfmn and ~solatron The solvent-free CH,CI, extract (48 g) of the ground plant (Soxhlet ) was stirred with Et,0 (800 ml,
1211
Short
1212
Reports
2 hr), left m the refrigerator overnight, filtered and solvent removed A small portlon of the Et,O-soluble fraction when subrnltted to TLC [n-hexane-Et,0 (2 I), 2 developments] gave 1 which was purified by further TLC (same solvent system) Another portion ofthe Et,O-soluble fraction when submitted to Silica gel CC (120 g packed m n-hexdne) gave nine fractions 1 [n-hexane-Et,0 (2 l)], 2-4 [n-hexane-EtZO(l l)J, 5-8 (Et,O) and 9 [CH,Cl,--MeOH (1 l)]. from whtch 24 were tqloated as follows Fiaction I, which contained-Z, was mitlaffy submltted to S1hca gel CC and the fraction eluted with n-hexane-Et,0 (4 1) gave 2 on further TLC [n-hexane-Et,O-AcOH (25 10 1)J Fractions 6-1 gave J when submItted to TLC [n-hexaneCHCI,-AcOH (10 10 3), 1 development] TLC of Fr 2 [n-hexane-Et,O-AcOH (159 1). 2 developments] gdve 4, 13C NMR (b, CDCI,) (for C-l to C-20, m order) 27 lo..f&l I., I.15 R 1444.. 17 9 IX 38 3, -ii 5 27 1,36.Q.. 37 9 rdr 38.3, 4Ll;385,!74,12~h,1424~1!10,!383,!722,!86or!8R,!57
and 18 6 or 18 8, m accord with the structure The spectral propertles of I 4 are deacrlbed
m the text
Ackmwle~en~rWe tWnk Dr S. P Mcbagldm for pJaoj collection and ldentlficatlon and Mr Peter Baker for mass spect!I:~ data This. work was sl_!pp~.!Ytedby the Nat!n.nI. Spcnce Foundation (Grant PCM-8304771)
A NEW CLERODANE
DERIVATIVE
REFERENCES
1 Bohlmann, F and Jakupovlc, J (1979) Ph~~tochemrstrv 18. I367 2 Dommguez, X A, Qumtero. G dnd Butrmlle D (1977) Phytochemzscrl 11, 1855 3 Hammouda, F, Rizk. A and FI Kddq. M S (1979) Pharmazle 34, 112 4. Tandon, S and Rastogl, R P (1979) Phytotkrmlctrv 18.494 5. Eohlmann,. F and Greoz, M (l-972). Chew. Bu- L)-5, IL?_? 6 Bohlmann. F and Wegner P (19X2) Phr~fochemr\lr\ 21, 1693 7 PaJJdey,. 11 C _ S1.n&_, A. K ,.lhrwl, N. c ,.Sh_harma & P .. Baruah, J N, Watanabe, K, Kulanthdivel P and Herz W (1984)Phytochemutrv 23, 39 1 8 Correll, D and Johnston. M (1970) Manuul oj the V~~sculur Plants of Trwa Texas Re\edrch Foundation. Renner Texas 9 Bohlmann. F and Mahantd, P (1979) Ph_vfo(herm,tr, 18. 1Oh7 10 Mlsra, R , Pandey. R and Dec. S (1964) 7i~rrahedrou Letrerr 49,375l 11 Waaner. H j Se&z, R. Chart Vi Latter. H nlld Hecr. W (I 977) Terruhedron Lrrter, 35 3039 12 Wasner~H,S&~,R-, Lorter, H nndHerz. W !!97R) J Qrq Chem 43, 3339 13 I.4
FROM
R K BHATT, JAMPANI B HANGMAN Department
of Chemlqtry,
Indian
(Reowd
Key Word Index---Tmospora
Abstract-A new clerodane estabhshed by spectroscopic
tordfolru,
Institute
B. K
CORDZFOLIA
SABATA*
Bombay
400076,
India
1987)
new clerodane
diterpencnd
has been Isolated from the stems of Tznospora cordlfoh means and by comparison with closely related clerodane derlvatlves
diterpenoid
INTRODUCTION
Chemical mvestlgation of Tmospora cordfolra has led to the isolation of a phenohc hgnan and one dlterpemc furano lactone which were reported earher [ 1,2] In the
*Author
and
of Technology,
receroed 21 August
Memspermaceae,
TINOSPORA
to whom correspondence
should
be addressed
Its structure
was
present paper the lsolatlon and structure of a new clerodane derlvatlve, Isolated from the same plant IS reported The structure (1) was deduced mamly with the help of ‘H NMR, spin-decouplmg and ‘“C NMR studies along with the comparison of the spectral data of closely related clerodane dlterpenords such as 6-hydroxy arcangehsm (2) [>.J, fi.&$~.~:.~.(3). [q., &h.y&@~y f‘.b.rs&r>n (_S). [>* 41 ’ palmarm (4) [S -71 and X-hydroxy columbm (5) [8]
0
DITERPENOIDSOF SHIVANAND
D. JOLAD,*
BARBARA
CONYZA COULTERI
N. TIMMERMANN, FERNANDO
Uiwersity
oi?Anzona,
U S A., *Umverslty
office
ol_And~ Lands
Studies,
JOSEPH J HOFFMANN, A
ROBERT
B. BATES?
and
CAMOU?
Bloresources
Research
Facility,
Z5U E Wencla
of Arizona, College of Pharmacy, Tucson, AZ X5721, U S A, tUmverslty
Tucson,
0031 ~9422/88 9300+000 1988 Pergamoo Journals Ltd
Road; l%cson,
of Arizona, Department
AZ K57U6;
of Chemistry,
AZ 85721, U S A.
(Recewed 24 June 1987) Key Wbrdrnd~x--C’onyza acid, 2P-hydroxyhardwlckuc
C’oulteri; Asteraceae, Astereae, acid, bacchotrlcuneatm A
Solidigmmae,
Abstract-Four furanodlterpenolds, mcludmg three furanoclerodanes, parts of Conyza Coulterl One of the terpenolds, 2fl-hydroxyhardwickuc first time
INTRODUCTION
The genus Conyza IS known to produce acetylenes, diand trlterpenolds, flavones and coumarms [l-7] This note reports our examination of the chemical constltuents of Conyza Coulterl Gray, an annual herb of the southwestern United States and Mexico that IS known to be toxic to hvestock [S]. From the methylene chloride extract of C Coultert, four furanodlterpenolds (l&4), mcludmg three furanoclerodanes (2-4) were isolated and characterized mainly by spectral (NMR and MS) methods and comparisons with literature data The furanodlterpenold (1) was identified [IR i~!$“: 3000-2500 and 1690 (COOH), 1500 and 870 (furan), 3040, 1645, 1635 (C=C) cm -‘; E MS m/z. 316 (M+), 81 (furan-&HZ), 69 ()=CHE H,, base); ‘HNMR as reported] as centlpedlc acid, a constituent of Centrpeda orbuhru (Asteraceae) [9]. The three furanoclerodanes include, hardwlcknc acid (2), bacchotrlcuneatin A (3) and 2/Ghydroxyhardwicklic acid (4). Compound 2, previously reported from plants of different genera [7,10], was identified by direct comparlson with an authentic sample Compound 3, previously isolated from Baccharls trrcuneata var. trumeata [l 1, 121 and B. artrcuhta [ 131, was characterized on the basis of 0 II its spectral data [IR nail’? 1770 and 1750 (X-O-), 3015 and 1660 (C=C), 1500 and 868 (furan) 1380 (Me) cm-‘; EIMS m/z. 342 (Mf ), 312 (base), 95 (furan-CH,-eH,), 94 (furan-CH=CH,); HRMS m/z 342 1540 (+ 5.3 mmu), CZ0HZ205 and ‘H NMR as previously reported]. 2P-Hydroxyhardwlckilc acid (4) was previously prepared (1) by the saponification of 2fl+uccmyloxyhardwlckuc acid present m the acidic fraction of Dodonaea boronfoh and characterized as its methyl ester derlvatlve and (n) by synthesis, along with Its C-2 eplmer, from ent-15,16-epoxycleroda-3,13(16),14-tr~ene-2~,19-d~ol lsolated from the neutral fraction of the same species [14]. Recently, Pandey, et al. [7] reported the C-2 eplmer of 4, characterized as Its methyl ester derivative, from Conyza japonica and synthesized both eplmers from methyl hard-
diterpenoidi,
centipedic
acid; Iiard.wlcknc
have been ldentlfied m the extract of the aerial acid, was found as a natural product for the
wlckilate. Our lsolatlon of 4 is the first report of the free acid from a natural source Its spectral data [IR Lz!:13. 3600 and 1020 (OH), 3000-2500 and 1700 (COOH), 1500 and 870 (furan), 3010, 1635 and 840 (C=C) cm-‘, EIMS m/z: 332 (M+ ), 314 (M-H,O), 95 (furan-CH,-&HZ), 81 (furan&H,), ‘H NMR (6, CDCI,) 0 75 (H-20), 0 84 d (J = 5 8 Hz, H-17), 1 20 (H-19), 4.34 br s (H-2), 6.26 br s (H14), 6 63d (5=4 1 Hz, H-3), 7.20 br s (H-16), 7.31 br s (H15)] parameters are m accord with those given for Its methyl ester derivative Cl43 In particular, the signal for H-2 as a doublet (J=4 1 Hz) rather than as a doublet of doublets (J = 2.5, 1 5 Hz) defines the configuration at C-2 [7] The ‘%Z NMR parameters for 4 (see Experimental), hitherto unreported, support the structure EXPERIMENTAL Pfant material. The collectlon of C. Coulterl was made on 30 August 1985 m the Santa Rota and Huachuca mountains m Southern Arizona A voucher specimen (SPM 3039) was deposited m the Herbarium of the Umverslty of Arizona All plant material was air-dried, ground to 3 mm particle size and stored at 5” prior to extraction Extracfmn and ~solatron The solvent-free CH,CI, extract (48 g) of the ground plant (Soxhlet ) was stirred with Et,0 (800 ml,
1211
Short
1212
Reports
2 hr), left m the refrigerator overnight, filtered and solvent removed A small portlon of the Et,O-soluble fraction when subrnltted to TLC [n-hexane-Et,0 (2 I), 2 developments] gave 1 which was purified by further TLC (same solvent system) Another portion ofthe Et,O-soluble fraction when submitted to Silica gel CC (120 g packed m n-hexdne) gave nine fractions 1 [n-hexane-Et,0 (2 l)], 2-4 [n-hexane-EtZO(l l)J, 5-8 (Et,O) and 9 [CH,Cl,--MeOH (1 l)]. from whtch 24 were tqloated as follows Fiaction I, which contained-Z, was mitlaffy submltted to S1hca gel CC and the fraction eluted with n-hexane-Et,0 (4 1) gave 2 on further TLC [n-hexane-Et,O-AcOH (25 10 1)J Fractions 6-1 gave J when submItted to TLC [n-hexaneCHCI,-AcOH (10 10 3), 1 development] TLC of Fr 2 [n-hexane-Et,O-AcOH (159 1). 2 developments] gdve 4, 13C NMR (b, CDCI,) (for C-l to C-20, m order) 27 lo..f&l I., I.15 R 1444.. 17 9 IX 38 3, -ii 5 27 1,36.Q.. 37 9 rdr 38.3, 4Ll;385,!74,12~h,1424~1!10,!383,!722,!86or!8R,!57
and 18 6 or 18 8, m accord with the structure The spectral propertles of I 4 are deacrlbed
m the text
Ackmwle~en~rWe tWnk Dr S. P Mcbagldm for pJaoj collection and ldentlficatlon and Mr Peter Baker for mass spect!I:~ data This. work was sl_!pp~.!Ytedby the Nat!n.nI. Spcnce Foundation (Grant PCM-8304771)
A NEW CLERODANE
DERIVATIVE
REFERENCES
1 Bohlmann, F and Jakupovlc, J (1979) Ph~~tochemrstrv 18. I367 2 Dommguez, X A, Qumtero. G dnd Butrmlle D (1977) Phytochemzscrl 11, 1855 3 Hammouda, F, Rizk. A and FI Kddq. M S (1979) Pharmazle 34, 112 4. Tandon, S and Rastogl, R P (1979) Phytotkrmlctrv 18.494 5. Eohlmann,. F and Greoz, M (l-972). Chew. Bu- L)-5, IL?_? 6 Bohlmann. F and Wegner P (19X2) Phr~fochemr\lr\ 21, 1693 7 PaJJdey,. 11 C _ S1.n&_, A. K ,.lhrwl, N. c ,.Sh_harma & P .. Baruah, J N, Watanabe, K, Kulanthdivel P and Herz W (1984)Phytochemutrv 23, 39 1 8 Correll, D and Johnston. M (1970) Manuul oj the V~~sculur Plants of Trwa Texas Re\edrch Foundation. Renner Texas 9 Bohlmann. F and Mahantd, P (1979) Ph_vfo(herm,tr, 18. 1Oh7 10 Mlsra, R , Pandey. R and Dec. S (1964) 7i~rrahedrou Letrerr 49,375l 11 Waaner. H j Se&z, R. Chart Vi Latter. H nlld Hecr. W (I 977) Terruhedron Lrrter, 35 3039 12 Wasner~H,S&~,R-, Lorter, H nndHerz. W !!97R) J Qrq Chem 43, 3339 13 I.4
FROM
R K BHATT, JAMPANI B HANGMAN Department
of Chemlqtry,
Indian
(Reowd
Key Word Index---Tmospora
Abstract-A new clerodane estabhshed by spectroscopic
tordfolru,
Institute
B. K
CORDZFOLIA
SABATA*
Bombay
400076,
India
1987)
new clerodane
diterpencnd
has been Isolated from the stems of Tznospora cordlfoh means and by comparison with closely related clerodane derlvatlves
diterpenoid
INTRODUCTION
Chemical mvestlgation of Tmospora cordfolra has led to the isolation of a phenohc hgnan and one dlterpemc furano lactone which were reported earher [ 1,2] In the
*Author
and
of Technology,
receroed 21 August
Memspermaceae,
TINOSPORA
to whom correspondence
should
be addressed
Its structure
was
present paper the lsolatlon and structure of a new clerodane derlvatlve, Isolated from the same plant IS reported The structure (1) was deduced mamly with the help of ‘H NMR, spin-decouplmg and ‘“C NMR studies along with the comparison of the spectral data of closely related clerodane dlterpenords such as 6-hydroxy arcangehsm (2) [>.J, fi.&$~.~:.~.(3). [q., &h.y&@~y f‘.b.rs&r>n (_S). [>* 41 ’ palmarm (4) [S -71 and X-hydroxy columbm (5) [8]