Highly oxygenated guaianolides from some compositae plants

The isolation of twenty new highly oxygenated guaianolidcs along with sc\'cral known guaianolidcs from Vernonia ark/1/t.Hllrct (aer-ial parts and n~ots), P.H!tulostijjiia kingii (:tcrial parts), Diconra anonrala (roots), H1·poc!tueris crete11si.\·, Sau.uurea mlidjiJ/ia, S. itn•olucrata, S. cundictms, Bislwpantltu.\· suliceps and 8/uinvi//ea latifolia (acri:tl parts) han· hccn rc\'icwcd. The sesquiterpene lactones are characteristic secondary metabolites of Compositae and their biological activities lac by intramolecular cyclization of r- or()... hydroxy acids and broadly termed as cyclic esters. The suf fix 'of ide' in their names to the lactone moiety in the molecule. The a.,B-unsaturated-y-lactones are cis- or trans fused to the C 6 -C 7 or C 8 -C 7 positions of the carbocyclic skeleton.The structural of the basic sesquiterpene the incorporation of an epoxy ring, hy groups, ester moieties and or oxidation of certain groups even opening of the rings. Acids in esterification and/or acids,

The sesquiterpene lactones are characteristic secondary metabolites of Compositae and their biological activities also make them of interest to pharmacologists. These lactones are formed by intramolecular cyclization of ror()... hydroxy acids and broadly termed as cyclic esters. The suffix 'of ide' in their names refers to the lactone moiety in the molecule. The a.,B-unsaturated-y-lactones are cisor transfused to the C 6 -C 7 or C 8 -C 7 positions of the carbocyclic skeleton.The structural variation of the basic sesquiterpene skeleton involves the incorporation of an epoxy ring, hydroxy groups, ester moieties and reduction or oxidation of certain groups or even opening of the rings. Acids generally involve in esterification are 4 and/or 5 carbon acids, viz. methacrylic, angelic, tiglic, senecioic, methylbutyric acids or their hydroxy and/or acetoxy derivatives. Guaianolides are derived from guaianc skeleton. In this short review, we present the results of structure elucidation of two guaianol ides from Vernonia arkansana 1 , the senecioate and the hydroxysenecioate guaianol ides from Pseudostiffi ia kingii 2 , a 9a-hydroxyguaianolide from Dicoma a noma/a sub sp. cirsioides 3 , a guaian-5, 12-olide along with its precursor from Hypochocris cretensis 4 , four II a-13-dihydro derivatives from Saussurea salicijvlia 5 L., an 8a-propionyloxydehydrocostus lactone from S. i11volucrata 5 , three chlorojanerin derivatives from S'. Calldicut1S 6 , nve highly oxygenated guaianolides from Bishopanlhus so/iceps 7 and a pumilin derivative from 8/aim·i//ea lali(hlia 8 . Vernonia arkansa11a DC. has been investigated ear-lier9·10. The re-investigation of roots afforded the known guaianol ides 1-6 11 along with a new one 7. The structure of 7 was clearly arrived from the 1 11 N"-'IR spectral data which were similar to that of deh) drozalu:t:min C 5. The stereochemistry ofC-8 '"as dedu...:l·d !rom couplings observed for ll-8 and li·om the typical dm\ 11 Jield sli i 1' 1 of I 1-13' proton. 1 ts molecular forrn ul~1 C 1 , 11 16  examination gave marginatin, three bourboncnolides and a new methoxyguaianolide 8. Its 1 r 1 N\1R data agree with its structure. From the signals ofH-13, the presence of a methylene lactone 1vas con tinned. llom.:ver, the absence of signals for H-6. 11-7 i nJ icated a 6, 7-double bond, its presence being supported by a downneld shift.:d dllublet e~t (i 2.86, which was coupled 1vith a bro<tckneJ double doublet at r5 2.26. These sign:ds probably \lt''t' tho~c: of Il-l and 11-5. A methoxy group was present al (_-I 0 and an acetoxy group at C-8 position. The ~lereochem is try at C-4 and C-1 0 was assigned by analogy to that ofbourbone1wlides and characterized as 8a-acetoxy-4;J-hydroxy-l Oa-methoxyguai-6.7.11( 13)-dienc:-6.12-olide. l'rohably lauonc could be: formed by fragmentation ofbourboncnolide 9 b) attach. of methanol at C-1 0 as shown in Scheme 1.-1 he bourhllnenolide 9 has simultaneously been isolated from this plan!. Pseudostifftia is a monotypic genus and belongs to the subtribe Pseudostifftinae 12 . Earlier work on Pseudostifftia kingii H. Robins led to the isolation of acetylenes and triterpenes 13 • The re-investigation of its aerial parts reported · the isolation ofknown guaianolides, viz. desacylcynaropicrin 10 14 , arguerin 8 11 15 , cynaropicrin 12 16 , 8a-hydroxydehydrozaluzanin C 7 1 , the corresponding 11,8,13-dihydroderivative 6 1 , as well as two further lactones, the senecioate 13 and the hydroxysenecioate 15. The structure of 13 was established from 1 H NMR data. Its NMR clearly showed the presence of a zaluzanin C derivative, as most signals were similar to those of zaluzanin C. However, an additional senecioyloxy residue was present.
Spin decoupling showed that this group had to be placed at C-8 while from the coupling constants the a-orientation could be established. Acetylation afforded the acetate 14 and 13 was identified as 8a-senecioyloxydehydrozaluzanin C. The 1 H NMR spectral data of 15 indicated that a hy-780 droxylated ester group was present. Since the signal of the olefinic methyl group was at 5 2.15, the stereochemistry was also clear. All other signals were similar to those ofl3. Acetylation gave the diacetate 1.6 and its 1 H NMR spectrum further established the structure. 15 was named as 8 a-  The 1 H NMR spectrum of 17 was very simi Jar to 5. The presence of a 9a-hydroxy group was deduced from the downfield shifts of H-14 (5.09 s, 4.67 d) and H-9 (4.63 ddd) and the value of coupling J 8 9 . This was confirmed by spin decoupling which allowed the assignment of all signals. The corresponding 9-0-angelate was isolated from Zinnia species 19 and as expected the couplings 1 8 . 9 were nearly the same. It was characterized as 9a-hydroxy-. dehydrozaluzanin C.
Earlier work on the genus Hypochoeris has shown that guaianolides related to lactucin may be characteristic for this genus 2 0-22 . The chemical examination of the aerial parts of Hypochoeris cretensis Benth. showed the presence of taraxasterol, lupeol and its acetate, phytol, isoalantolactone and a new guaian-5, 12-olide 18 and the corresponding precursor 19.
The structure of 18, which on addition of diazomethane afforded the pyrazoline 20, was derived from the molecular formula and the high field 1 H NMR spectrum.
The presence of a methylene lactone followed from the typical pair of down field signals at 5 6.62 and 5.71. The IR band at 1740 cm-1 indicated a ~lactone. The chemical shifts of two olefinic methyls and a quartet at 56.18 showed that most likely a guaianolide with a keto group at C-2 and a 1(10) as well as a 3,4-doublc bonds were present. The absence of a H-5 signal and the results of spin decoupling clearly showed that a 5, 12-guaianolidc was present, which 13 0 18 19 required an equatorial orientation ofH-7. Accordingly, this signal was narrowly split only as all. couplings were small. Inspection of a model further showed that the angles H-7-H-13 supported the observed small couplings ofH-13. The stereochemistry of the pyrazoline derivative 20 was deduced from the observed downfield shift of H-6,8. The 1 H NMR spectral data of 19 showed that a methyl ester was present. The conformation was clearly different from that of 18 since H-7 was now axial as followed from the couplings observed. Spin decoupling allowed the assignment of all signals. Guaian-5,12-olide 18 was named as hypocretenolide and its precursor 19 as methyl hypocretenoate.
The large genus Saussurea (Compositae, tribe-cynareae) with more than 300 species 23 has been investigated chemically for acetylenes 24 as well as for sesquiterpene lactones. d f .
The structures of 25 and 27 were followed from the 1 H NMR spectra which indicated that these compounds only differed in the nature of the ester groups. The typical exomethylene signals in the spectrum of cynaropicrin were replaced by a methyl doublet at o 1.13 and a doublet quartet at o2.77. Accordingly, these lactones were 11,13-dihydro derivatives of cynaropicrin and of the corresponding 4hydroxytiglate. The configuration at C-11 was followed from the coupling J 7 11 (7Hz), while a very similar compound with a J 1 a-methyl showed as usual a large coupling 25  were replaced by a methyl doublet at o 1.14 and a doublet quartet at 2.74. Subsequently, these lactones were 11,13dihydro derivatives of the previously isolated methylene lactones. Again the coupling J 7 11 exhibited the presence of 11 ,8-methyl groups. The lacto~es 26 and 28 were identified as lla,13-dihydrojanerin and 1la,l3-dihydrodesacyljanerin-4-hydroxytiglate, respectively. The structure of propionate 32 could be easily deduced from the 1 H NMR spectrum which was very dose to that of the corresponding acetate 35    The structure of 48 could easily be deduced from the 1 H NMR spectrum which was close to that ofdehydroleucodin 41 and in part to that of 47 42 . The configuration at C-8 and C-9 followed from the observed couplings and the relative position of the ester group from the chemical shifts of H-8 and H-9. From spectral data it was characterized as 5desoxypumilin.