Studies on the Synthesis of Sesquiterpene Lactones, 16. The Syntheses of 11β,13-Dihydrokauniolide, Estafiatin, Isodehydrocostuslactone, 2-Oxodesoxyligustrin, Arborescin, 1,10-Epiarborescin, 11β,13-Dihydroludartin, 8-Deoxy-11β,13-dihydrorupicolin B, 8-Deoxyrupicolin B, 3,4-Epiludartin, Ludartin, Kauniolide, Dehydroleucodin, and Leucodin

Andô, Masataka; Ibayashi, K.; Minami, Naoki; Nakamura, Tomomasa; Isogai, Koji; Yoshimura, H.

doi:10.1021/np50106a001

Cited by 38 publications

(24 citation statements)

References 33 publications

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“…(ϩ)-Costunolide, dehydrocostus lactone, and parthenolide (22; Sigma, St. Louis) were dissolved in ethanol at 10 mm concentrations. A sample of leucodin (19) was kindly provided both by Prof. M. Ando (Niigata University, Niigata City, Japan; Ando et al, 1994) and Dr. Shi Yong Ryu (Korea Research Institute of Chemical Technology, Yusung, Taejon, Korea), who also provided its C 11 -epimer achillin (Ho et al, 1998). 11,13-Dihydro-dehydrocostus lactone (mokko lactone) was a gift of Prof. Y. Asakawa (Tokushima Bunri University, Tokushima, Japan).…”

Section: Methodsmentioning

confidence: 99%

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Biosynthesis of Costunolide, Dihydrocostunolide, and Leucodin. Demonstration of Cytochrome P450-Catalyzed Formation of the Lactone Ring Present in Sesquiterpene Lactones of Chicory

et al. 2002

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Chicory (Cichorium intybus) is known to contain guaianolides, eudesmanolides, and germacranolides. These sesquiterpene lactones are postulated to originate from a common germacranolide, namely (ϩ)-costunolide. Whereas a pathway for the formation of germacra-1(10),4,11(13)-trien-12-oic acid from farnesyl diphosphate had previously been established, we now report the isolation of an enzyme activity from chicory roots that converts the germacrene acid into (ϩ)-costunolide. This (ϩ)-costunolide synthase catalyzes the last step in the formation of the lactone ring present in sesquiterpene lactones and is dependent on NADPH and molecular oxygen. Incubation of the germacrene acid in the presence of 18 O 2 resulted in the incorporation of one atom of 18 O into (ϩ)-costunolide. The label was situated at the ring oxygen atom. Hence, formation of the lactone ring most likely occurs via C 6 -hydroxylation of the germacrene acid and subsequent attack of this hydroxyl group at the C 12 -atom of the carboxyl group. Blue light-reversible CO inhibition and experiments with cytochrome P450 inhibitors demonstrated that the (ϩ)-costunolide synthase is a cytochrome P450 enzyme. In addition, enzymatic conversion of (ϩ)-costunolide into 11(S),13-dihydrocostunolide and leucodin, a guaianolide, was detected. The first-mentioned reaction involves an enoate reductase, whereas the formation of leucodin from (ϩ)-costunolide probably involves more than one enzyme, including a cytochrome P450 enzyme.Chicory (Cichorium intybus), also known as French endive, Witloof, and succory is probably a native of Europe and Asia. At present, this composite plant is mainly cultivated for its roots (C. intybus var sativum) that contain high amounts of inulin (a Fru polymer) or for its sprouts (C. intybus var foliosum Hegi) that are a well-known salad crop (Vogel et al., 1994;Kruistum, 1997;Westerdijk, 2000). The white sprouts, which are grown in the dark, have a slightly bitter taste that is associated with the presence of sesquiterpene lactones. These compounds occur throughout the plant, though at highest levels in the roots (0.42% dry weight), and act as deterrents toward insects (Rees and Harborne, 1985;Price et al., 1990).Sesquiterpene lactones are a major class of plant secondary metabolites that are mainly found in the Asteraceae but also occur infrequently in other high plant families and lower plants (Seigler, 1998). The majority of the more than 4,000 known different structures has a guaiane, eudesmane, or germacrane framework. Also the sesquiterpene lactones of chicory belong either to the guaianolides, eudesmanolides, or germacranolides ( Fig. 1; Seto et al., 1988;van Beek et al., 1990). (ϩ)-Costunolide (Fig. 2, 15) is structurally the simplest of all germacranolides and is generally accepted as the parent compound of the three mentioned types of sesquiterpene lactones (Geissman, 1973; Fischer et al., 1979;Seaman, 1982; Fischer, 1990).Our studies with chicory roots have made it apparent that its sesquiterpene lactones are derived from (ϩ)-germa...

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Section: Methodsmentioning

confidence: 99%

“…We thank Prof. M. Ando (Niigata University, Niigata City, Japan; Ando et al, 1994) and Dr. S.Y. Ryu (Korea Research Institute of Chemical Technology, Yusung, Taejon) for the gift of leucodin and Prof. Y. Asakawa (Tokushima Bunri University, Tokushima, Japan) for the gift of dihydro-dehydrocostus lactone.…”

Section: Acknowledgmentsmentioning

confidence: 99%

Biosynthesis of Costunolide, Dihydrocostunolide, and Leucodin. Demonstration of Cytochrome P450-Catalyzed Formation of the Lactone Ring Present in Sesquiterpene Lactones of Chicory

et al. 2002

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“…The comparison of the 1 H and 13 C NMR chemical shift data with those in the literature [11] as well as the Nuclear Overhauser effect (NOE) experiment data for 5 revealed that compound 5 was identical to 8-acetylarteminolide isolated from Artemisia sylvatica [11] [11]}; this result may imply that the relative configurations of 5 and 8-acetylarteminolide were identical, while their absolute configurations remained unexplained. Compounds 6 and 7 were guaianolide sesquiterpenes, identified as dehydroleucodin [12] and dehydromatricarin A [13], respectively. The eudesmanolide sesquiterpenes, 8 and 9, were identified as santamarin [14][15][16] and reynosin [17,18], respectively.…”

Section: Resultsmentioning

confidence: 99%

Flavonoids and sesquiterpenoids, constituents from Eupatorium capillifolium, found in a screening study guided by cell growth inhibitory activity

Sadhu

Hirata

et al. 2006

J Nat Med

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“…as a colorless solid; mp 140–142°C (lit. : 145°C 34, 140°C 38, 39; [α] D = + 60° ( c = 4.1, CHCl 3 ) (lit. : + 63° (CHCl 3 ) 34, + 60° (CHCl 3 ) 38, + 55° (MeOH) 40; R f = 0.49 (hexane/EtOAc, 7:3); MS (ESI, MeOH): m / z = 271.2 ([M + Na] + ); anal.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Antitumor‐Active Arglabin Derivatives

Csuk

Heinold

Siewert

et al. 2011

Archiv der Pharmazie

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Arglabin derivatives varied at the endo- or exo-cyclic double bond were synthesized and studied in a colorimetric sulforhodamine B assay for their cytotoxicity. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α-methylene-γ-butyrolactone moiety led to compounds of similar or only slightly reduced cytotoxicity but different, cell line-dependent selectivity. In addition, arglabin is an excellent starting material for the synthesis of the guaianolide arborescin.

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Cited by 38 publications

References 33 publications

Biosynthesis of Costunolide, Dihydrocostunolide, and Leucodin. Demonstration of Cytochrome P450-Catalyzed Formation of the Lactone Ring Present in Sesquiterpene Lactones of Chicory

Biosynthesis of Costunolide, Dihydrocostunolide, and Leucodin. Demonstration of Cytochrome P450-Catalyzed Formation of the Lactone Ring Present in Sesquiterpene Lactones of Chicory

Flavonoids and sesquiterpenoids, constituents from Eupatorium capillifolium, found in a screening study guided by cell growth inhibitory activity

Synthesis and Biological Evaluation of Antitumor‐Active Arglabin Derivatives

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