- Chromones and coumarins from Saposhnikovia divaricata (Turcz.) Schischk. Growing in Buryatia and Mongolia and their cytotoxicity
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Ethnopharmacological relevance: Saposhnikovia divaricata (family Apiaceae) a traditional medicinal plant distributed in many provinces of China, is well known for the pharmaceutical value and has been used for rheumatic arthritis, and anxiety in children. Antiviral, antioxidant and antiproliferative activities were also mentioned. The application of this plant are recorded in the Chinese Medicine (CM) classical text the Shen Nong's Materia Medica (Shen Nong Ben Cao Jing). In this monograph S. divaricata (syn Radix Ledebouriella divaricata) is graded as a premium-grade herb, with their broad-spectrum of therapeutic applications for the treatment of cough, common cold, arthralgia, as well as in rheumatic disorders. Aim of the study: To isolate and identify chemical constituents (chromones and coumarins) from S. divaricata, collected in Buryatia and Mongolia and to study their in vitro anticancer activity against MEL-8, U-937, DU-145, MDA-MB-231 and ВТ-474 cell lines. Materials and methods: An 40% aqueous ethanol extract of the roots of S. divaricata was prepared and further successively fractionated by extraction with petroleum ether, diethyl ether, tert-butyl methyl ether and ethyl acetate. The obtained extracts were subjected to a series of chromatographic separations on silica gel for isolation of individual compounds. Isolated compounds were tested for their cytotoxicity with respect to model cancer cell lines using the conventional MTT assays. Results: Total of 15 individual compounds: coumarins scopoletin 2, bergapten 3, isoimperatorin 4, marmesin 5, (+)-decursinol 9, (?)-praeruptorin B 10, oxypeucedanin hydrate 11, chromones: hamaudol 6, cimifugin 7, 5-О-methylvisamminol 8, chromone glycosides: prim-O-glucosylcimifugin 12, sec-O-glucosylhamaudol 13, 4′-O-β-D-glucopyranosyl-5-О-methylvisamminol 14, 4′-O-β-D-glucopyranosylvisamminol (15) and also polyyne compound panaxinol 1 were isolated and characterized. The structure of dihydropyranocoumarin 10 was confirmed by X-ray diffraction analyses. HPLC-UV method was used for determination of the content of most abundant chromones 7, 12 and 14 in the roots of S. divaricata, collected in Mongolia. Compounds 3–11 and 13, 14 were evaluated for their cytotoxicity with respect to model cancer cell lines. All the compounds were non-toxic in the hemolysis test. Conclusion: This report about the phytochemical profiles of S. divaricata growing in Mongolia and Buryatia led to the identification of 14 compounds including coumarins and chromones. The available coumarins and chromones may serve as new leads for the discovery of anticancer drugs.
- Frolova, Tatyana S.,Ganbaatar, Jamsranjav,Petrova, Tatyana N.,Pokrovskii, Andrey G.,Radnaeva, Larisa D.,Rybalova, Tatyana V.,Shults, Elvira E.,Taraskin, Vasilii V.,Urbagarova, Bayarma M.
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- Therapeutic evaluation of synthetic peucedanocoumarin III in an animal model of Parkinson’s disease
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The motor and nonmotor symptoms of Parkinson’s disease (PD) correlate with the formation and propagation of aberrant α-synuclein aggregation. This protein accumulation is a pathological hallmark of the disease. Our group recently showed that peucedanocoumarin III (PCIII) possesses the ability to disaggregate β sheet aggregate structures, including α-synuclein fibrils. This finding suggests that PCIII could be a therapeutic lead compound in PD treatment. However, the translational value of PCIII and its safety information have never been explored in relevant animal models of PD. Therefore, we first designed and validated a sequence of chemical reactions for the large scale organic synthesis of pure PCIII in a racemic mixture. The synthetic PCIII racemate facilitated clearance of repeated β sheet aggregate (β23), and prevented β23-induced cell toxicity to a similar extent to that of purified PCIII. Given these properties, the synthetic PCIII’s neuroprotective function was assessed in 6-hydroxydopamine (6-OHDA)-induced PD mouse models. The PCIII treatment (1 mg/kg/day) in a 6-OHDA-induced PD mouse model markedly suppressed Lewy-like inclusions and prevented dopaminergic neuron loss. To evaluate the safety profiles of PCIII, high dose PCIII (10 mg/kg/day) was administered intraperitoneally to two-month-old mice. Following 7 days of PCIII treatment, PCIII distributed to various tissues, with substantial penetration into brains. The mice that were treated with high dose PCIII had no structural abnormalities in the major organs or neuroinflammation. In addition, high dose PCIII (10 mg/kg/day) in mice had no adverse impact on motor function. These findings suggest that PCIII has a relatively high therapeutic index. Given the favorable safety features of PCIII and neuroprotective function in the PD mouse model, it may become a promising disease-modifying therapy in PD to regulate pathogenic α-synuclein aggregation.
- Ham, Sangwoo,Kim, Heejeong,Yoon, Jin-Ha,Kim, Hyojung,Song, Bo Reum,Choi, Jeong-Yun,Lee, Yun-Song,Paek, Seung-Mann,Maeng, Han-Joo,Lee, Yunjong
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- ISOSAMIDIN ANALOG AND SAMIDIN ANALOG PRODUCTION METHOD
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PROBLEM TO BE SOLVED: To provide a simple method of industrial-scale production of an isosamidin analog or samidin analog. SOLUTION: In the production method, a compound represented by the formula (1) in the figure is 1) senecioylated and 2) acetylated. [X is O or the like; R1 are each independently a C1-3 alkyl group or the like; R2 is H or the like; R3 are each a C1-3 alkyl group; m is an integer from 0 to 2; n is 1 or 2; and the symbol * represents an asymmetric center.] SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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- Determination of the Absolute Configuration of Khellactone Esters from Peucedanum japonicum Roots
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Sixteen new angular dihydropyranocoumarins (1-16) and 24 known compounds were isolated from the roots of Peucedanum japonicum Thunb. The absolute configuration of diacylkhellactone was established by partial hydrolysis, the Mosher method, and X-ray crysta
- Hong, Min Jee,Kim, Jinwoong
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p. 1354 - 1360
(2017/06/01)
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- Antidiabetic effect, antioxidant activity, and toxicity of 3′,4′-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats
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Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3′,4′-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15?mg/kg (p?50) >2000?mg/kg and, at this dose, no signs of toxicity or death were reported after 14?days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested.
- Domínguez-Mendoza, Elix Alberto,Cornejo-Garrido, Jorge,Burgue?o-Tapia, Eleuterio,Ordaz-Pichardo, Cynthia
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supporting information
p. 4086 - 4091
(2016/08/01)
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- Improved Biological Activities of Isoepoxypteryxin by Biotransformation
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Isoepoxypteryxin is the major coumarin of a Japanese medicinal plant Angelica shikokiana. This research was designed to study the effect of structural changes through fungal biotransformation on the reported biological activities of isoepoxypteryxin. Among the tested microorganisms, only Cordyceps sinensis had enzymes that could catalyze the ester hydrolysis and the reductive cleavage of the epoxide ring of isoepoxypteryxin, separately, to give two more polar metabolites (+)-cis-khellactone (P1) and a new coumarin derivative (+)-cis-3′-[(2-methyl-3-hydroxybutanoyl)oxy]-4′-acetoxy-3′,4′-dihydroseselin (P2), respectively. The polar metabolite P2 showed stronger cytotoxicity and higher selectivity than isoepoxypteryxin. On the molecular level, P2 showed more in vitro inhibition of both tubulin polymerization and histone deacetylase 8 (HDAC8). Similarly, P2 showed more neuroprotection against amyloid beta fragment 1 – 42 (Aβ1 – 42)-induced neurotoxicity in human neuroblastoma cells (SH-SY5Y) and exhibited more inhibition of the in vitro aggregation of Aβ1 – 42. Both metabolites showed stronger antiplatelet aggregation by increased inhibition of thromboxane-A2 synthase (TXS) activity and thromboxane-A2 (TXA2) production. This study is the first to describe the improved cytotoxic, neuroprotective, and antiplatelet aggregation activities of isoepoxypteryxin through its biotransformation by C. sinensis.
- Mira, Amira,Amen, Yhiya M.,Alkhiary, Wael,Zhu, Qinchang,Nakagawa, Toshinori,Tran, Hai-Bang,Shimizu, Kuniyoshi
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p. 1307 - 1315
(2016/12/21)
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- Towards heterogeneous organocatalysis: Chiral iminium cations supported on porous materials for enantioselective alkene epoxidation
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Enantiomerically pure iminium cations have been supported on a microporous support (zeolite Y) and on a mesoporous support (Al-MCM-41). These materials are effective asymmetric catalysts for the epoxidation of a range of aryl alkenes, giving high conversions quickly and with enantioselectivities similar to or in some cases even higher than are achievable using the corresponding iminium tetraphenylborates under homogeneous conditions. The catalysts can be simply recycled by filtration and washing. The methodology is illustrated in the synthesis of two natural products, (-)-(3′S)-lomatin and (+)-(3′S,4′R)-trans-khellactone, showing the general efficacy of our approach. The Royal Society of Chemistry 2013.
- Bulman Page, Philip C.,Mace, Andrew,Arquier, Damien,Bethell, Donald,Buckley, Benjamin R.,Willock, David J.,Hutchings, Graham J.
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p. 2330 - 2339
(2013/09/02)
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- Enantioseparation and absolute configuration determination of angular-type pyranocoumarins from Peucedani radix using enzymatic hydrolysis and chiral HPLC-MS/MS analysis
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Angular-type pyranocoumarins from Peucedani Radix (Chinese name: Qian-hu) have exhibited potential for use on treatment of cancer and pulmonary hypertension. Due to the existence of C-3′ and C-4′ chiral centers, compounds belonging to this chemical type commonly exist in enantiomers and/or diastereoisomers, which may elicit distinct activities during their interactions with the human body. In the present study, a new method, which combines enzymatic hydrolysis with chiral LC-MS/MS analysis, has been developed to determine the absolute configurations of these angular-type pyranocoumarins. Pyranocoumarins isolated from Qian-hu, their enantiomers, or metabolites were individually incubated with rat liver microsomes. As the common end product from enzymatic hydrolysis of all tested pyranocoumarins, cis-khellactone was collected and its absolute configuration was determined by comparison with (+)-cis-khellactone and (-)-cis-khellactone using chiral LC-MS/MS. The absolute configurations of all tested parent pyranocoumarins were determined by combination of LC-MS/MS, NMR and polarimetric analysis. The results revealed that the metabolite cis-khellactone retained the same absolute configurations of the stereogenic carbons as the respective parent compound. This method was proven to be rapid and sensitive and also has advantages in discriminating single enantiomers and mixtures of optical isomers with different ratios.
- Song, Yue-Lin,Zhang, Qing-Wen,Li, Ya-Ping,Yan, Ru,Wang, Yi-Tao
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experimental part
p. 4236 - 4251
(2012/07/27)
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- 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins: A new class of P-glycoprotein modulators
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Objectives P-glycoprotein (Pgp) overexpression in tumour cells leads to multidrug resistance (MDR) and causes failure in cancer chemotherapy. We have previously identified (±)-praeruptorin A (PA) as a potential lead compound for Pgp modulators. In this study we investigated the MDR-reversing activities of PA derivatives. Methods Series 7,8-pyranocoumarins with various C-3′ and C-4′ side chains had been semi-synthesized and their MDR-reversing activity was investigated in Pgp-overexpressing MDR tumour cell line HepG2/Dox and in a KB V1 xenograft animal model. Key findings All 7,8-pyranocoumarins exhibited equal or higher activity in modulating Pgp. DCK (12), DMDCK (15), 16, 21, 23 and 24 at 4 μm achieved 91%~99% decrease in IC50 value (concentration inhibiting cell growth by 50%) of anticancer agents vinblastine, doxorubicin, puromycin and paclitaxel, and were more active than others. DMDCK also remarkably enhanced the growth inhibitory effect of paclitaxel on KB V1 xenografts (P 0.05), showing a potency required for clinical usage. Mechanistic studies suggested that these 7,8-pyranocoumarins might reverse Pgp-MDR through directly binding to substrate binding site(s) or allosteric site(s) on Pgp therefore impairing Pgp-mediated drug transport. Conclusions Results from the study suggested that 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins could serve as a new class of Pgp modulator. Acyls play an important role in maintaining and enhancing the Pgp-modulating ability of pyranocoumarins. 3,4-Dimethoxyl substituted aromatic acyls, bearing a methoxy that might interact with Pgp as hydrogen bond accepter, were shown to be the most potent for reversing MDR. 2011 The Authors. JPP
- Shen, Xiaoling,Chen, Guangying,Zhu, Guoyuan,Cai, Jiazhong,Wang, Lu,Hu, Yingjie,Fong, Wang-Fun
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experimental part
p. 90 - 100
(2012/07/01)
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- Characterization of metabolism of (+)-praeruptorin B and (+)-praeruptorin E in human and rat liver microsomes by liquid chromatography coupled with ion trap mass spectrometry and time-of-flight mass spectrometry
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Peucedani Radix is a Chinese medicinal herb noted for its effects on treatments of respiratory and pulmonary disorders. As a part of a systematic pharmacokinetic evaluation of the herb in our laboratory, the present study investigated, for the first time, the metabolic profile of (+)-praeruptorin B (dPB) and (+)-praeruptorin E (dPE), two main bioactive constituents of Peucedani Radix in pooled liver microsomes of rats (RLMs) and humans (HLMs). dPE was eliminated faster than dPB in both species. The incubation of dPB with RLMs and HLMs resulted in eight (B1-B8) and nine (B1-B9) metabolites, respectively, while both RLMs and HLMs converted dPE into 13 metabolites (E1-13). Structures of all the metabolites were proposed through comparing their mass data obtained via tandem mass spectrometry on an MSD ion trap system (IT-MS/MS) coupled with high-resolution mass measurement by time-of-flight mass spectrometry (TOF-MS) with those of the respective parent compound. B1 and E1 were unambiguously identified as (-)-cis-khellactone. The formations of all the metabolites were NADPH-dependent. Oxidation and hydrolysis were demonstrated to be two predominant metabolic pathways of dPB and dPE. Oxidation initiated at either the C-3′ or C-4′ substituent, while hydrolysis only started from the C-3′ substituent. Fragmentation of all metabolites followed similar pathways to those of the parent pyranocoumarins. The information on metabolic properties of dPB and dPE and the mass fragmentation profiles of their metabolites obtained in the present study will aid in characterization of metabolic profiles of other angular-type pyranocoumarins and further investigation of in vivo fates of these pyranocoumarins and the herb. Copyright
- Song, Yue-Lin,Yan, Ru,Jing, Wang-Hui,Zhao, Hai-Yu,Wang, Yi-Tao
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experimental part
p. 719 - 730
(2012/02/02)
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- Highly enantioselective total synthesis of (-)-(3'S)-lomatin and (+)-(3'S,4'/?)-frans-khellactone
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Concise highly enantioselective three-step syntheses are described for (-)-(3'S)-lomatin and (+)-(3'S,4'fl)-frans-khellactone from 7-hydroxy- coumarin in 97% ee and in 57% and 58% overall yields, respectively, using nonaqueous enantioselective epoxidation
- Page, Philip C. Bulman,Appleby, Louise F.,Day, David,Chan, Yohan,Buckley, Benjamin R.,Allin, Steven M.,McKenzie, Michael J.
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supporting information; experimental part
p. 1991 - 1993
(2009/09/08)
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- Plant Coumarins. 3. (-temp)-PTeryxin from Peucedanum terebinthaceum
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The potentially medically valuable pyranocoumarin (+)-pteryxin was isolated for the first time from Peucedanum terebinthaceum Fischer et Turcz. The structure of (+)-pteryxin was rigorously proved using mass spectrometry, NMR, IR, and UV spectroscopy and c
- Ganbaatar,Gantumur,Osadchii,Shul'ts,Shakirov,Tolstikov
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experimental part
p. 578 - 581
(2009/04/07)
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- (±)-3′-O, 4′-O-dicynnamoyl-cis-khellactone, a derivative of (±)-praeruptorin A, reverses P-glycoprotein mediated multidrug resistance in cancer cells
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P-glycoprotein (Pgp) is an ATP-driven membrane exporter for a broad spectrum of hydrophobic xenobiotics. Pgp-overexpression is a common cause of multidrug resistance (MDR) in cancer cells and could lead to chemotherapeutic failure. Through an extensive he
- Shen, Xiaoling,Chen, Guangying,Zhu, Guoyuan,Fong, Wang-Fun
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p. 7138 - 7145
(2008/02/02)
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- A concise route for the synthesis of biologically interesting pyranocoumarins - Seselin, (±)-cis-khellactone, (±)- quianhucoumarin D, and the (±)-5-deoxyprotobruceol-I regioisomer
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An efficient synthesis of pyranocoumarins is achieved starting from 2H-pyrans. This process provides naturally occurring seselin, cis-khellactone, quianhucoumarin D, and the 5-deoxyprotobruceol-I regioisomer. Georg Thieme Verlag Stuttgart.
- Lee, Yong Rok,Lee, Won Kyong,Noh, Seok Kyun,Lyoo, Won Seok
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p. 853 - 859
(2007/10/03)
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- Coumarins from the fruits of Seseli devenyense
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Eight new coumarins were isolated from the fruits of Seseli devenyense Simonkai. Their structures were established from NMR and mass data and their absolute configurations from chemical degradation correlation reactions. The new structures are the decanoic and dodecanoic esters of (+)-lomatin (3, 4), the decanoates of (+)-cis-khellactone at positions 4′ (5) and 3′ (6) as well as the 2′S epimer of 8-(2,3-dihydroxy-3-methylbutyl)-7- hydroxychromen-2-one (7) named devenyol, its two O-monoglucosides at positions 3′ and 7 named devenyosides A (8) and B (9), and the corresponding 3′- and 7-O-diglucoside named devenyoside C (10). This plant is an interesting example of stereochemical diversity based on biodiversity given that other members of the Apiaceae family produce exclusively the 2′R epimers of compounds 7-9.
- Widelski, Jarek,Melliou, Eleni,Fokialakis, Nikolas,Magiatis, Prokopios,Glowniak, Kazimierz,Chinou, Ioanna
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p. 1637 - 1641
(2008/09/17)
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- Absolute stereostructures of acylated khellactone-type coumarins from Angelica furcijuga
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Two new acylated khellactone-type coumarin hyuganoside I (1) and hyuganin F (2) were isolated from the leaves of Angelica furcijuga. Their absolute stereostructures were determined on the basis of chemical and physicochemical evidence. Furthermore, the absolute stereostructures of the acyl moieties in hyuganins A (3) and C (4) and isoepoxypteryxin (5) were elucidated.
- Morikawa, Toshio,Matsuda, Hisashi,Ohgushi, Teruki,Nishida, Norihisa,Ishiwada, Tomoko,Yoshikawa, Masayuki
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p. 2211 - 2215
(2007/10/03)
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- A new pyranocoumarin from Peucedanum praeruptorum
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A new dihydropyranocoumarin was isolated from the root of Peucedanum pareruptorum and the structure were established as 3'(R)-isobutyryloxy-4′(R)-acetoxy-3′,4′-dihydroseselin (1) by spectroscopic methods. The absolute configuration was deduced by chemical correlations with known compounds.
- Kong, Ling-Yi,Li, Yi,Niwa, Masatake
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p. 1915 - 1919
(2007/10/03)
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- Two dihydropyranocoumarins from Peucedanum wawrii
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Two dihydropyranocoumarins were isolated from the root of Peucedanum wawrii and the structures were established as 3′(R)-acetoxy-3′,4′-dihydroxanthyletin (1) and 3′(R)-acetoxy-4′(S)-angeloyloxy-3′,4′-dihydroseselin (2), respectively, by spectroscopic meth
- Kong, Ling-Yi,Wu, Xian-Li,Niwa, Masatake
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p. 599 - 606
(2007/10/03)
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- Medicinal foodstuffs. XX. Vasorelaxant active constituents from the roots of Angelica furcijuga Kitagawa: Structures of hyuganins A, B, C, and D
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From the methanolic extract with vasorelaxant activity obtained from Angelica furcijuga Kitagawa, four new khellactone-type coumarins, hyuganins A, B, C, and D, were isolated together with twelve known coumarins, two known acetylenic compounds, and a known lignan. The structures of hyuganins A, B, C, and D were determined on the basis of chemical and physicochemical evidence. Nine principal coumarins (hyuganin A, anomalin, pteryxin, isopteryxin, isoepoxypteryxin, praerosides II and IV, apiosylskimmin, (R)-peucedanol 7-O-β-D-glucopy-ranoside), two acetylenic compounds [(-)-falcarinol and falcarindiol], and related compounds were examined for inhibitory activities on high concentration of K+ (High K+)- and dl-norepinephrine (NE)-indueed contractions. The results indicate that the 3'- and 4'-acyl groups of khellactone-type coumarins are essential for the inhibitory activity on the contractions by High K+. Hyuganin A and anomalin showed inhibitory effects on High K+-induced contraction, but not on NE-induced contraction. Other active coumarins (pteryxin, isopteryxin, isoepoxypteryxin) and an acetylenic compound (falcarindiol) non-selectively inhibited both contractions by High K+ and NE.
- Matsuda,Murakami,Nishida,Kageura,Yoshikawa
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p. 1429 - 1435
(2007/10/03)
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- Natural product-like combinatorial libraries based on privileged structures. 3. The "libraries from libraries" principle for diversity enhancement of benzopyran libraries
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As described in the preceding two papers, our interest in the construction of natural and natural product-like libraries for chemical biology studies led to the development of a new solid-phase cycloloading strategy for the construction of substituted benzopyrans. Herein, we report a parallel solution-phase method that facilitates the enhancement of both the size and diversity of these non-oligomeric benzopyran libraries using the "libraries from libraries" principle. We examine the rationale behind the use of this tandem strategy to construct discrete small molecule libraries, and describe the development of a polymer-assisted solution-phase (PASP) methodology necessary to effect the required transformations. Once developed, this chemistry is applied to two demonstration libraries.
- Nicolaou,Pfefferkorn,Barluenga,Mitchell,Roecker,Cao
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p. 9968 - 9976
(2007/10/03)
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- Qianhucoumarin I from Peucedanum praeruptorum
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A new angular dihydropyranocoumarin, named qianhucoumarin I was isolated from the root of Peucedanum praeruptorum. By spectral analysis and chemical evidence, the structure was elucidated as 3'(S)-acetoxy-4'(S)-tigloylilxy- 3',4'-dihydrosesetin, and the absolute configurations were established by chemical correlation with known compounds.
- Kong, Ling-Yi,Min, Zhi-Da,Li, Yi,Li, Xian,Pei, Yue-Hu
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p. 1689 - 1691
(2007/10/03)
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- Asymmetric synthesis of 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK), a potent anti-HIV agent
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An efficient asymmetric synthesis of 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) (1) via catalytic asymmetric dihydroxylation is reported. Among seven commercial ligands investigated, (DHQ)2-PYR is the most enantioselective ligand for the catalytic asymmetric dihydroxylation of seselin (5), a synthetic intermediate of DCK, and affords up to 86% e.e.
- Xie,Crimmins,Lee
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p. 4529 - 4532
(2007/10/02)
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- Anti-AIDS Agents. 15. Synthesis and Anti-HIV Activity of Dihydroseselins and Related Analogs
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Forty-two dihydroseselins based on the structure of suksdorfin (1) were synthesized in order to evaluate their anti-HIV activity.These synthetic derivatives include 3',4'-di-O-acyl- and 3'- or 4'-O-acyl-cis-dihydroseselins (8-21) and 3',4'-trans-dihydroseselins with O-acyl and/or O-alkyl groups at the 3' and 4' positions (6, 22-43).Two 4'-azido (44, 45) and three 4'-alkylamido (46, 48, 49) derivatives were also prepared.By using optically pure reagents, three pairs of diastereoisomers were synthesized and separated as optically pure compounds (14, 15; 16, 17; 38, 39).Together with the above synthetic derivatives, seselin (3) and (+/-)-cis- (4), (+)-cis- (5), and (+/-)-trans-dihydroseselin-3',4'-diol (7) were also tested for their in vitro anti-HIV activity.An optically pure compound, 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (16), showed potent inhibitory activity and remarkable selectivity against HIV replication.The EC50 value and in vitro therapeutic index (TI) of 16 are 4 x 10-4 μM and 136 719, respectively, which are better than those shown by AZT in the same assay.In addition, compound 16 is also active against HIV replication in a monocytic cell line and in peripheral blood mononuclear cells (PBMCs).Our in vitro assay indicated that, like compound 1, compound 16 is not an inhibitor of HIV-1 reverse transcriptase.Moreover, the anti-HIV activity of 16 is stereoselective as its three diastereoisomers (17, 38, 39) are at least 10 000 times less active.Since other synthetic dihydroseselin derivatives with different substituents or without any substituents are inactive or are active only at much higher concentractions, the antiviral potency of 16 could be associated with the camphanoyl moieties of its structure.Therefore, compound 16 represents a unique coumarin structure with promising anti-HIV activity.
- Huang, Li,Kashiwada, Yoshiki,Cosentino, L. Mark,Fan, Sharon,Chen, Chin-Ho,et al.
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p. 3947 - 3955
(2007/10/02)
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- Natural Product Chemistry. Part 181. Investigations on the Synthesis of Dihydropyrano- and Dihydrofurano-coumarins by Application of Catalytic Enantioselective cis-Dihydroxylation
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As part of a study on the applicability of catalytic enantioselective cis-dihydroxylation for the synthesis of dihydropyrano- and dihydrofurano-anellated coumarins new routes to (-)-cis-khellactone 1b, (-)-trans-khellactone 1c and rutaretin 4 have been developed.
- Reisch, Johannes,Voerste, Arnd A. W.
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p. 3251 - 3256
(2007/10/02)
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- DIHYDROPYRANOCOUMARINS FROM PEUCEDANUM JAPONICUM
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Two new angular-type dihydropyranocoumarins, peujaponisinol A and B, were isolated from the roots of Peucedanum japonicum and the structures determined as 3'(S)-senecioyloxy-4'(S)-hydroxy-3',4'-dihydroseselin and 3'(S)-hydroxy-4'(S)-senecioyloxy-3',4'-dihydroseselin, respectively, by spectroscopic and chemical methods.
- Ikeshiro, Yasumasa,Mase, Izumi,Tomita, Yutaka
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p. 1543 - 1545
(2007/10/02)
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- DIHYDROPYRANOCOUMARINS FROM ROOTS OF PEUCEDANUM JAPONICUM
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Two new angular-type dihydropyranocoumarins, peujaponisin and (-)-visnadin, were isolated from the roots of Peucedanum japonicum and the structures determined as 3'(S)-senecioyloxy-4'(S)-isovaleryloxy-3',4'-dihydroseselin and 3'(S)-2-methylbutyryloxy-4'(S
- Ikeshiro, Yasumasa,Mase, Izumi,Tomita, Yutaka
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p. 4303 - 4306
(2007/10/02)
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- SYNTHESIS OF (+/-)-PRAERUPTORIN A AND RELATED KHELLACTONE DERIVATIVES
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The first synthesis of the pyranocoumarin natural product, (+/-)-praeruptorin A (= Pd-Ia), is described.A general method for the preparation of various khellactone derivatives is reported.
- Bal-Tembe, Swati,Bhedi, Dilip N.,Souza, Noel J. de,Rupp, Richard Helmut
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p. 1239 - 1249
(2007/10/02)
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- JUNOSMARIN, A NEW KHELLACTONE ESTER FROM CITRUS JUNOS TANAKA
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A new (-)-trans-khellactone ester, junosmarin, was isolated from the root bark of Citrus junos (Rutaceae) and the structure was assigned as 1 on the basis of spectral data and synthesis of its acetate 5.
- Ju-ichi, Motoharu,Inoue, Mami,Tsuda, Rika,Shibukawa, Naomi,Furukawa, Hiroshi
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p. 2777 - 2779
(2007/10/02)
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- COUMARIN SULPHATES OF SESELI LIBANOTIS
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Three new sulphate ester salts derived from known coumarin alcohols - one of them tertiary - have been obtained from roots of Seseli libanotis subsp. eu-libanotis.Their structures were established as (2'S)-rutaretin-1''-sulphate, (3'R)-lomatin-3'-sulphate and (3'R,4'R)-khellactone-3'-sulphate.They were together with their parent alcohols characterized by 13C NMR spectroscopy.It is the first report on coumarin sulphates in plants.Key Word Index - Seseli libanotis subsp. eu-libanotis; Umbelliferae; dihydrofurocoumarins; dihydropyranocoumarins; coumarin sulphates; sulphate ester salts; FDMS; 13C NMR.
- Lemmich, John,Shabana, Marawan
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p. 863 - 866
(2007/10/02)
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- COMPARATIVE CHARACTERIZATION OF THE COUMARIN COMPOSITION OF Seseli campestre GROWING IN MOLDAVIA AND IN THE CAUCASUS
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The results are given of the identification of (-)-trans-khellactone and its 4'-methyl ether and (-)-3'(S),4'(S)-trans-3'-senecioyloxy-4'-angeloyloxy-3',4'-dihydroseselin and of the establishment of the structure of three new khellactone derivatives - campestrol (VII), C19H22O6, D20+32 deg (c 7.8; chloroform), campestrinol (X), C24H26O7, mp 116-118 deg C, and campestrinoside (I), C20H24O10, mp 172-173 deg C, D -272.5 deg (c 4.7; ethanol).It has been shown on the basis of chemical and spectral characteristics that campesol, earlier described as a new substance, is a mixture of two isomeric compounds - 4'-hydroxy-3'-senecioyloxy-3',4'-dihydroseselin and 3'-angeloyloxy-4'-hydroxy-3',4'-dihydroseselin.
- Abyshev, A. Z.,Sidorova, I. P.,Abyshev, D. Z.,Florya, V. N.,Zmeikov, V. P.,Kerimov, Yu. B.
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p. 400 - 407
(2007/10/02)
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