THE FLAVONOIDS O F P A R T H E N I U M L. JAMES A. MEARS Phytochemislry Laboratory, Academy of ~ V a t u r aScieitces l of Philadelphia Ansm\cr.--The distribution of 34 flavonoids detected in the Korth American species of Pnrthenzitni L. is presented. Of the 27 flavonoids identified (some tentatively) all are flavonols: eight are based on kaernpferol, seven on quercetin, four on &hydroxykaempferol and eight on the quercetagetin skeleton. Of the 34 flavonoids detected, 19 are glycosides and 15 are aglycones, primarily highly methylated compounds.
Partheizium I,. is a genus of the Asteraceae (Compositae) long considered to be part of the llelampodiinae but recently included with the ragweeds in the Ambrosiinac (1). Tlie biologj- and chemistry of Partlzeizium has been of interest because P. argeiitatum Gray (guayule) is a desert species \vliich is a source of natural rubber (2) and P. hysteropliorus I,. (Santa l l a r i a feverfew, mule\\-eed) causes severe contact dermatitis (3, 4, 5). Tlie sesquiterpene lactone chemistry of the genus has been well summarized (6, i, 8 ) , and several papers (9, 10, 11) have provided information about flavonoid? of several species of the genus. Here t!!e results of an examination of the flavonoid constituents of all the S o r t h American species of Partheizium are correlated with the earlier published data.
RESULTS The distribution of 34 flavonoid,q detected in S o r t h American Partheiiium species is shown in table 1. The proposed structures of 2'7 of the flavonoids are indicated in figure 1. All the proposed structures are flavonols: derivatives of lcaempferol (XIII, XIV, XIX-XXII, XXVII, XXT'III), quercetin (IX, XV, XVIII, XXIII-XXF'I), 6-hydroxykaempferol (11, VII, YIII, XVI), and quercetagetin (111-VI, X-XII,
XVII). Partheizium tomeittosum DC. is cliaracterized here as a species of t\\-o varieties: P . tomeirtosunt var. tometitosum and P . tonzeiztosum var. stramonium (Greene) Rollins. Only a few derivatives of quercetin and quercetagetin \\-ere detected in var. tome~ztosz~m, although Rodriguez (1 1 ) reports other minor components. llinor components \\-ere detected in many taxa but are not iricluded liere unless they occurred sufficiently frequently to be regarded as dependable taxonomic units. T\\-o unidentified glycosides ivere also detected in var. tometitosum. Similarly, only :: fe\v derivatives of kaempferol and quercetagetin \\-ere detected in var. stramonium. Partlieizium fruticosum Less is also composed of t\vo varieties (12) : var. f r u t i cosum and var. trilobatum Rollins. One aglycone derivative of quercetagetin and three glycoside derivatives of kaempferol and quercetin \\-ere detected in var. jruticoszm. Six aglycones, derivatives of cjuercetngetin, quercetin, 6-hydroxyIcaempferol, kaempferol and 1;aempferol 3-methj-1 ether, arid three glycosides, derivatives of quercetagetin and quercetin, \\-ere detected in var. trilobatum. Parthciiizim lozaiiiaizum Blake, \\-Iiich is very closely related to P . f r u t i c o s z ~ mvar. trilobatum, produces niucli the same pattern as P. fruticosuin var. trilobatum, except that liaenipferol 3-methyl ether \\-as not detected in Y.lozariiauz~m. Partheiiiunz schnttii Greenman, ivhicli is endemic to limestone in Yucatan, \\-as found t o produce only one flavonoid, quercetagetin 3,i-dimethyl ether; Iioivever, it is possible that fresher material would result in a richer species pattern. 708
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FIGURE 1 . Proposed structures of flavonoids of P a r f h e n i z m . R4
R2 h e R
0 H
Compounds
R1
RP
OGLY OCH,
OCH, OH OCH3 OCHs OH OH OCHj H OCH, OCH, OCHa H H H OCH, OCH: H H H H
I1 I11 1111-1 TI1 TI11 IX
x
XI XI1 XI11 XI1XT
XI.1 XTII XI211 XIX-XXII xxIII-XxvI XXTII-XX;\?II
0 RS
R4
R5 OH OH
OH OCH, OH OH OH
OH
OCHI OGLT
OGLT
OH OH OH OGLT
OCH3 H OH OCH? H OH H
OCHs OH OCH, OH OH OCHs OH OH OH OH OH OH
Parthetiium rollitisiaiizim Rzedon-ski morphologically links the sections Partheiiichaeta and Bolophytzrm of Rollins (12). hlthough Rodriquez (1 1 )detected five flavonoid aglycones and eleven glycosides, the samples analyzed here showed no glycosides. The aglycones are all derivatiwq of quercetagetin, 6-hydrouykaempferol, and quercetin. Rodriguez also reported ( I 1) glycosides of quercetin and quercetagetin derivatives. I n northern Mexico and western Texas Partlietzium illcatizLm HBK. hybridizes n-ith Y.argeiztatzim Gray. Man\- of the desert populations show some signs of combinations of the characters ~vhiclidistinguish mesic forms of P . ilzcatizkm from the desert limestone forms of P . argetitatzim. The few samples of P. iticatziim n-hich showed little morphological evidence of influence by argeiitafzm characters produced a flavonoid pattern n-ith only one aglycone, kaempferol 3-methyl ether, and with eight flavonoid glycosides, derivatives of quercetin. quercetagetin and kaempferol. The several samples of P. argt.)ztatum shojving little evidence of influence by P . i i l c a t i t l f i z characters produced a flavonoid pattern rich in aglycones and glycosides: derivatives of quercetagetin. 6-hydrosyl;aempferol, quercetin. kaenipferol and kaempferol 3-methyl ether. The many intermediate samples showed individually and collectively a strongly complementary pattern of seven aglycone derivatives of quercetagetin, G-hydroxyl;aenipferol, quercetin, lciempferol and kaempferol 3-methyl ether and thirteen glycoside derivatives of all those structural types except G-hydroxykaempferol.
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TABLE 1. Distribution of 34 flavonoids detected in S o r t h iimerican Parthenzum'
.x
h: L.
c -
T.iX.4.. .. ........ SECT. P A R T H E S I C H A E T A P . lomenlosum2.. . . . . . . . . . . . . . . . . . . var. lomentosum.. . . . . . . . . . . . . . var. stramonirrm.. . . . . . . . . . . . . . . . P . frulicosum~.. . . . . . . . . . . . . . . . var. fruticosum . . . . . . . . . . . . . . . . . var. trilobatum . . , . . , , , . P . lozanianum.. , . , , , . . , . , , . , . , , , , . . P. schollii.. . . . . . . . . . . . . . . . . . . . . . P . rollinsianum.. . . . . . . . . . . . . . . . . . . . P . iticattum.. . . . . . . . . . . . . . . . . . . . . . . . P . argentalum. . . . . . . . . . . . . . . . . P . argentalum X incairum . . . . . . . .
0
-
SECT. BOLOPH I'TU.11 P. alpinum.. ....................... P . letraneuris. . . . . . . . . . . . . . . . . . . . . . . P . ligidalum... . . . . . . . . . . . . . . . . . . .
0
-
SECT. PARTHE.VIASTRC.11 P . i1iteg~ifolium2. . . . . . . . . . . . . var. integrifolium ......... var. henryanum. . . . . . . . . . . . . vm. mabrjanum. . . . . . . . . . . . var. auriculalum. ...... var. hispidum . . . . . . . . . . . . . . . . . . f.repens., . . . . . . . . . . . . . . . . P . radfordii.. . . . . . . . . . . . . . . . . . . . .
0
0
0
0
-
0 ~
0 0
_-
0 0 0 0 --
SECT. ARGYROCHAET.4 P. coriferfum~. . . . . . . . . . . . . . . r a r . coiifcrtum, . . . . . . . . . . . . . . var. dizaricatiim . . . . . . . . . . . var. lgratum.. . . . . . . . . . . . . . . . Tar. microcephalum.,. . . . . . . . . P. densipilum . . . . . . . . . . . . . . . P. biOrnnali,hdum . . . . . . . . . . . . . . P. hysterophorus,. . . . . . . . . . . . . . . . .
___
0
.-
0 0
0 0 v c
0
c
0 C
0
0
0
'Filled circles indicate compounds regularly detected in a talon as a major component; hollon circles indicate Compounds detected as minor components or olten mifsing in a t a l o n . R I values ITBA. 15'; IIOAr' are given lor all unknonn and incompletely identified compounds. I n t h e names of t h e flavonoids, I i , Q , and Qg are used lor kaempferol, quercetin and quercetagetin, respectively. ? T h e use of filled and holloiv circles to indicate patterns lor those species in n-hich varieties v e r e studied represents 6 synthesis of t h e d a t a for t h e varieties studied.
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T IBLE 1. Distribution of 34 flavonoids detected in S o r t h -4merican Partheniuml
~o io
0 0 01
0 0 0 0
SI
' 0
0 , v -.
0
" -, 0 ,-.
O ' C 0 ' 3
,
I
v
- /-I-
'
0
-_ 1
-
C
ll
is d
0 0 0
"'
0
'v
n r
r
0 IS 0 0 0 0 ,-. v 0 0 3 0
-
-
0 0 0 0
0 0 0 0 0 0
0 0
0
-
-
c 3
3
c
3 I
" -,
0 -
~
The forementioned Ypecie- are all the Ypecie- of Rollin-' -ection Parflreiiichueta DC. except P. ~ z i ~ e ~ u c e Rolliniim of Bolivia Rodriguez (11) noted the occurrence of both aglj cone4 and glycoside- in P . ciueracezinz. but no -truerural types have been reported. Section Parfheriicliaefa is cliaracterized b\ a n ide \-ariety of aglycone and glycoqide derivative- of methylated and unmethylated derivative, of
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quercetagetin, quercetin, 6-hydroxykaempferol, kaempferol and kaempferol 3methyl ether. Parthenium alpinum (Suttall) Torrey & Gray. P. ligulatum (Jones) Barneby and P. tetraizeuris nameby-.three species of the temperate (western U.S.) section Bolophytum (Suttall) Torrey & Gray, were characterized earlier (9) as producing methylated aglycones and glycosides of quercetagetin and 6-hydroxj-kaempferol. Compound XPII, detected in P. tetraneuris and P. alpimrm, is a flavonol, 3,6-0methylquercetagetin 7-0-glycoside; it was earlier reported erroneously to be a flavone, 6-methoxyluteolin 7-0-glycoside. A previously undetermined constituent of P. alpinum and P. tetraizeuris has been identified tentatively, on the basis of chromatographic data, with 3,7,3’-tri-O-methylquercetagetin,which m-as reported by Rodriguez (11) from P. bipinnatifidum and P. hysterophorus. The t x o species and five other subspecific taxa of section Partheiziastrum DC. are very similar in flavonoid chemistry, Ti-ith the more widespread varieties showing more minor constituents : aglycones of quercetagetin, 6-hydrox;~kaempferol~ quercetin and kaempferol derivatives and glycosides of 6-hydroxykaempferol, quercetin and kaempferol derivatives. Some of the varieties and forms of P. integrifoliuvz L. produce very feu- detectable flavonoids. Var. integrifolium produces five aglycones and nine glycosides; var. heiiryanum Nears, four aglycones and four glycosides; var. mabryawm Nears, one aglycone and four glycosides of kaempferol; var. auriculatum (Britton) Cornelius ex Cronquist, tn-o aglycones and eight glycosides; var. hispidum (Rafinesque) Nears f . hispidum, three aglycones and nine glycosides; and var. hispidum f . repens (Eggert) Mears, one aglycone and tn-o glycosides of kaempferol. Some varieties and forms of P. integrijolium do not produce detectable amounts of flavonoids oxygenated at C6. Parthenium radfordii Nears produces two aglycones (6-hydroxy-3,i-di-O-metliy1 kaempferol and kaempferol 3-methyl ether) and six glycosides (glycosides of kaempferol, kaempferol 3-methyl ether and quercetin). Section Argyrochaeta (Cavanilles) DC. of Rollins (12) contains four North American species, P. coilfertum (Gray) Gray, P. densipilum Wooton, P. hysterophorus L., and P. bipinizati$dum (Ortega) Rollins, as well as P. glomeratum Rollins, which is endemic to northwestern Argentina and Bolivia. Parthenium confertum consists of several varieties: var. confertum, characterized by hi-o flavonoid aglycones and four glycosides, derivatives of quercetagetin and kaempferol; var. divaricatum Rollins, by five aglycones (derivatives of quercetagetin, 6-hydroxykaempferol and quercetin) and no glycosides (derivatives of 6-hydroxykaempferol, quercetin and kaempferol) ; var. lyratum (Gray) Rollins, by four aglycones (derivatives of quercetagetin, 6-hydroxykaempferol and kaempferol 3-methyl ether) and four glycosides (derivatives of kaempferol and quercetin) ; var. microcephalum Rollins, by three aglycones (derivatives of quercetagetin and 6-hydroxykaempferol) and five glycosides (derivatives of quercetin and kaempferol) . Parthenium densipilum, a very rare limestone endemic very closely related to P. confertum, is characterized by three aglycones (derivatives of quercetagetin, ti-hydroxykaempferol and kaempferol 3-methyl ether) and five glycosides of quercetin and kaempferol. Parthenium bipinnatifidum is characterized by seven aglycones (derivatives of quercetagetin, 6-hydroxykaempferol and kaempferol3-methyl ether) and ten glycosides of quercetagetin, quercetin, and kaempferol derivatives. Its very close relative P. glomeratum Rollinq, which n-as not examined in this study, was reported by Shen et al. (10) to produce a subset of the flavonoids of P . bipinnatijidum. Parthenium hysterophorus, which is very closely related t o both P. bipinnati$dum and
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P . glonteratum, differs from P. bipi?iuatifidum in a fen- detail;; P . hysteroplzorus is cliaracterized by six aglycones (derivativec of quercetagetin, 6-hydroxykaempferol, kaempferol and kaempferol 3-niethyl ether) and ten glycosides of quercetagetin, quercetin and kaempferol derivative.. Section -4rgyrochaeta DC. of Rollins. is therefore characterized by the presence of many aglycones of all four major structural type; as well as by the preqence of glycosides of quercetagetin, quercetin and kaempferol derivative.. A11 of the sections of Partlzenium recognized by Rollins (12) contain some species n-hich produce many aglycones and many glycosides except section Bolophytum, n-hich produce. primarily aglycone., with a fen- glycosides in P. tetrauewis. Similarly* all the sections tend to produce both the usual flavonoids, kaenipferol and quercetin derivatires, as well ac the C6-oxygenated types, except section Bolopiz3tum, which doe. not produce flavonoid2 that are not oxygenated ( 2 6 . Some varieties and forms of P. ititegrifolium (section Partheniastrum) do not produce detectable amount; of &oxygenated flavonoids. illtliough the flavonoid pattern of eyer- taxon is dictinct in some detail. there is little evidence of major difference3 in sectional trends in flavonoid structures. The tendency for forming methylethers and for &oxygenation in qection Bolopiiytum iq the most distinctive feature of the flavonoid chemistry of Partlieuium.
PROCEDURES Air-dried leaf material (100 g) of 1 to 20 population samples of each of the Partheniiim taxa included in table 1 was ground in 85% aqueous methanol. After extraction (24 hrj, the filtered solution n-as dried i n zacuo and separated into a chloroform-soluble fraction and a methanolwater-soluble fraction. The fractions were separated into components by tn-o-dimensional paper chromatography on Whatman 3 mm paper, developed first in TBA and second in 15% acetic arid. The color of the chromatographic components was recorded when viewed above a broad n-ave-length uv lamp with and without ammonia vapor present. Individual spots were eluted with methanol and were rechromatographed, cochromatographed o r analyzed by standard uv spectral procedures (13, 14, 15). Glycosides were hydrolyzed with 6 5 aqueous HCl. The aglycones were analyzed spectrally as before or were demethylated n-ith the pyridine-HBr method of Rosler (see 16) for co-chromatographic comparison with authentic samples or with demethylated types of known aglycones. Kilogram quantities of dried material of P . bipinnati.fidum, P . hTsterophoriis, P.incanuni, P . integrzfoliuni, and P. fruticosum var. trilobatunz n-ere extracted for polyclar column chromatography with various combinations of chloroform, butanone, methanol, and q-ater for elution. Identification of flavonoids and coumarins was by comparison of chromatographic and spectral data of both glycosides and aglycones with those reported for known structures. The chromatographic and uv spectral data for the 34 flavonoids are given in table 2. BCHKOWLEDGlIENTS Some of this study of the flavonoids of Partheniunz was accomplished during my graduate studies in the Phytochemistry Laboratories of the Botany Department of the University of Texas at Austin (directed by T. J. Mabry), but the greater part of this study was accomplished a t the Phytochemical Laboratory of the Botany Department of The Academy of Natural Sciences of Philadelphia. These studies relate to several traineeships and grants: NIH traineeship 5 TO1 M-OOi89 (to T. J. Mabry) and SSF grants GB-262i6 and GB-3i6G6. I thank Margaret Buckby, Helgard Siremberg, Elaine Bishop, Carole Ram, Roy Hill, and, particularly, Helen R. Mears, for laboratory assistance over a period of years. Helen R. Mears produced the figure for this paper. Receited 7 -\-oLeniber 1979. BIBLIOGRAPHY 1. T. Ptuessy, Contrib. Gray Herb. Harr. Tnzrt. 203, 65 (1973). 2. F. E. Lloyd, Guayule (Parthenium argentatum Gray). A Rubber-plant of the Chihuahuan Desert. Carnegie Inst. Washington Publ. 139 (1911). 3. S.W.French, Mil. Surgeon, 66, GT3 (1930). 4. A. Lonkar, B. .A. Tagasampagi, C. R . Sarayanan, A. B. Landge and D. D. Sawaikar, Confact Dermatzfzs, 2, 151 (1976). 5. E. Rodriguez, 31. 0. Dillon, T. J. Mabry, J. C. llitchell and G. H. N. Towers, Erperzentia, 32, 23G (19TGj.
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18. 19.
E. Rodriguez, H. Toshioka and T. J . hlabry, Phytochemisfrp, 10, 1145 (1971). E. Rodriguez, H. Yoshioka and T. J. Mabry, Ret. Lefznoanzer. Qztznz., 3, 184 (1972). .J 4 hlears, Proc. d c a d . .Tat. Sci. Piiila., 132 (1980). in press. J . .4 Mears, Phpfochemzsfry, 12,2265 (1973). 31. C. Shen, E. Rodriguez, K. Bern and T. J. Rlabry, Phytociiemzstrq, 12, 2265 (197G). E Rodriguez, Biociient. Syst. Ecol., 5 , 207 (19i7). R. C. Rollins, Contr. Gray Herb. H u n . L-me., 172, 1 (1950). T. J. Mabry, K. R. Markham and hl. B. Thomas, T h e Systematzc Identz-ficetion of Flezonozds. Springer-Verlag, Berlin. (1970). J . A. Mears and T. J. hlabry, Piiytociienzistry, 11, 411 (1972). J. D. Bacon, T. J . Mabry and J. A. Mears, Rea. Latinoanzer. @ m i . , 7, 83 (1976). G. Hovard and T. J. Mabry, Phytochenzistry, 9, 2413 (1970). J . B. Harborne, T. J. hIabry and H. Mabry, T h e Flavonoids. -4cademic Press. London and Kew York (1975). H. Rosler, A. Star and T. J. Mabry, Phytochemistrp, 10, 450 (1971). J. B. Harborne, C o i n p a r a h e Biochemistry of the Flaelonozds, Academic Press, London
20.
W. Herz, S. V. Bhat, H. Crawford, H. Wagner, G. hlaurer and L. Farkas, Phgiochenmtry,
21.
11, 372 (1972). A. G. Valesi, E. Rodriguez, G. Yander T-elde and T. J. Llabry, P i i y t o c h e m s f r y , 11, 2821 (1972).
I .
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