- Synthesis and antiproliferative activity of benzofuran-based analogs of cercosporamide against non-small cell lung cancer cell lines
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A novel series of 3-methyl-1-benzofuran derivatives were synthesized and screened in vitro for their antiproliferative activity against two human NSCLC cell lines (NSCLC-N6 mutant p53 and A549 wild type p53). Most promising compounds presented a structural analogy with the west part of cercosporamide, a natural product of biological interest. In particular, compounds 10, 12 and 31 showed cytotoxic activities at micromolar concentrations (IC50 50 values (25-40 μM).
- Bazin, Marc-Antoine,Bodero, Lizeth,Tomasoni, Christophe,Rousseau, Bénédicte,Roussakis, Christos,Marchand, Pascal
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Read Online
- An Efficient Regioselective Synthesis of 8-Formylhomoisoflavonoids with Neuroprotective Activity by Enhancing Autophagy
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6-Formylisoophiopogonone B (7a) and 8-formylophiopogonone B (7b), two natural products isolated fromOphiopogonjaponicus, represent a subgroup of rare 6/8-formyl/methyl-homoisoflavonoid skeletons. Herein we report an efficient method for the synthesis of these formyl/methyl-homoisoflavonoids. The synthesized compounds were evaluated for their neuroprotective effects on the MPP+-induced SH-SY5Y cell injury model and showed marked activity. Exploration of the neuroprotective mechanisms of compound7bled to an increased expression of autophagy marker LC3-II and down-regulation of autophagy substrate p62/SQSTM1. Molecular docking studies showed that7bmay prevent the inhibition of the classic PI3K-AKT-mTOR signaling pathway by interfering with the human HSP90AA1.
- Li, Jie,Yang, Fan,Zeng, Lin-Wei,Zhang, Fang-Min,Zhou, Chang-Xin,Gan, Li-She
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Read Online
- Biological Investigation of a Water-Soluble Isoginkgetin-Phosphate Analogue, Targeting the Spliceosome with In Vivo Antitumor Activity
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The first total synthesis of the natural product Isoginkgetin as well as four water-soluble Isoginkgetin-phosphate analogues is reported herein. Moreover, the full study of the IP2 phosphate analogue with respect to pharmacological properties (metabolic and plasmatic stabilities, pharmacokinetic, off-target, etc.) as well as in vitro and in vivo biological activities are disclosed herein.
- Letribot, Boris,Nascimento, Megane,Cerrato, Giulia,Darrigrand, Romain,Salgues, Valerie,Renko, Dolor,Pruvost, Alain,Alami, Mouad,Messaoudi, Samir,Apcher, Sebastien
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p. 4633 - 4648
(2022/03/27)
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- Anti‐melanogenic properties of velutin and its analogs?
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Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti‐inflammatory, anti‐allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti‐melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2‐diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural‐derived functional materials to regulate melanin synthesis.
- Choe, Jung-Won,Heo, Hee-Young,Jung, Se-Hui,Kim, Jaehyun,Lee, Kooyeon
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- Synthesis and Biological Evaluation of 4-Substituted Kaempfer-3-ols
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The synthesis of two series of five kaempfer-3-ols was described. The first set all have a C-3 hydroxyl group and the second has a carboxymethoxy ether at the C-3 position. Both series have variable substitution at the C-4 position (i.e., OH, Cl, F, H, OMe). Both kaempferols and carboxymethoxy ethers were evaluated for their ability to inhibit ribosomal s6 kinase (RSK) activity and cancer cell proliferation.
- Kim, Sugyeom,Lannigan, Deborah A.,Li, Yu,Lin, Lin,O'Doherty, George A.,Sayasith, Peyton R.,Tarr, Ariel T.,Wright, Eric B.,Yasmin, Sharia
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p. 4279 - 4288
(2020/04/09)
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- Design, synthesis and antiproliferative activity evaluation of fluorine-containing chalcone derivatives
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A series of new chalcones containing fluoro atom at B ring have been designed, synthesized, and evaluated to be antiproliferative activity against a panel of human tumor cell lines. Some of the analogs (8, 9, 12, 45, 46 and 48) displayed powerful antiproliferative effects to certain human tumor cells, but all of them were devoid of any cytotoxicity towards the normal HEK 293. Acridine orange staining data supported that the cytotoxic and antiproliferative effects of the synthesized analogs on tumor cells are mediated through apoptosis. The compounds 12 and 46 manifested concentration-dependent antiproliferative activity in human hepatocellular carcinoma cell lines using an xCELLigence assay. The structures and antiproliferative activity relationship were further supported by in silico molecular docking study of the compounds against tubulin protein which suggests our compounds interference to cell division. Communicated by Ramaswamy H. Sarma.
- Aktas Anil, Derya,Algul, Oztekin,Burmaoglu, Serdar,Duran, Nizami,Gobek, Arzu,Kilic, Deryanur,Yetkin, Derya
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- Discovery of a series of selective and cell permeable beta-secretase (BACE1) inhibitors by fragment linking with the assistance of STD-NMR
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Two β-secreatase (BACE1) inhibitors from natural products (cinnamic acid and flavone) were linked to furnish potent, cell permeable BACE1 inhibitors with noncompetitive mode of inhibition, with the assistance of saturated transfer difference (STD)-NMR technique. Some of these conjugates also exhibited selective BACE1 inhibition over other aspartyl proteases such as BACE-2 and renin, as well as poor cytotoxicity. Taken together, conjugates 4 represent a new series of BACE inhibitors warrants further investigation for their potential in Alzheimier's disease therapy.
- Fang, Wei-Shuo,Sun, De-yang,Yang, Shuang,Cheng, Chen,Moschke, Katrin,Li, Tianqi,Sun, Shanshan,Lichtenthaler, Stefan F.,Huang, Jian,Wang, Yinghong
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supporting information
(2019/09/30)
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- New homoisoflavonoid analogues protect cells by regulating autophagy
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As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.
- Gan, Li-She,Zeng, Lin-Wei,Li, Xiang-Rong,Zhou, Chang-Xin,Li, Jie
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supporting information
p. 1441 - 1445
(2017/03/08)
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- Synthesis of methylated quercetin analogues for enhancement of radical-scavenging activity
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Three quercetin derivatives with enhanced radical-scavenging activity were designed and synthesised. Because the radical-scavenging reaction of quercetin is known to proceed via an electron transfer from quercetin to radicals, producing the corresponding quercetin radical cation intermediate, the introduction of electron-donating groups into the quercetin molecule is expected to enhance its radical-scavenging activity. Thus, methyl groups were introduced into the catechol moiety in the quercetin molecule at either the 2′- or 5′-position, or both. All three quercetin analogues were found to exhibit higher radical-scavenging activity than the parent quercetin. The activity of 5′-methylquercetin is the highest among the three analogues. The optimised structure of 5′-methylquercetin calculated by density functional theory demonstrated a coplanar structure between the 4H-curomen (AC rings) and catechol (B ring) moieties, while dimethylquercetin and 2′-methylquercetin have a twisted structure between the AC and B rings. These results demonstrate that the highest radical-scavenging activity of 5′-methylquercetin is due to the stabilisation of the radical cation intermediate by the electron-donating effect of the methyl group as well as by the planar structure of the molecule.
- Imai, Kohei,Nakanishi, Ikuo,Ohkubo, Kei,Ohba, Yusuke,Arai, Takuya,Mizuno, Mirei,Fukuzumi, Shunichi,Matsumoto, Ken-ichiro,Fukuhara, Kiyoshi
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p. 17968 - 17979
(2017/03/31)
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- Synthetic method for isorhamnetin
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A provided synthetic method for isorhamnetin comprises the following steps: step 1, protecting 2,4,6-trihydroxyacetophenon with benzyl, so as to synthesize 2,4,6-tribenzyloxyacetophenone; step 2, performing addition reaction on 2,4,6-tribenzyloxyacetophenone and vanillin and then removing the protection group, so as to obtain 3'-methoxy-4',5,7-trihydroxychalcone; step 3, performing catalytic hydrogenation to remove a protection group; and step 4, employing an oxidation agent potassium peroxymonosulfate aqueous solution to perform oxidation cyclization reaction on 3'-methoxy-4',5,7-trihydroxychalcone. Isorhamnetin is synthesized by employing the above four steps, technology operation is simple, production cost is low, and the obtained product is high in purity and easy for industrialized production.
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Paragraph 0020; 0021; 0022; 0026; 0027; 0031; 0032-0042
(2016/10/10)
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- Total Synthesis of the Antiviral Natural Product Houttuynoid B
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The first total synthesis of houttuynoid B, a powerful antiviral flavonoid glycoside from the Chinese plant Houttuynia cordata, is described. In a key step, a Baker-Venkataraman rearrangement employing an already glycosylated substrate was used to efficiently set up the fully functionalized carbon skeleton. The required benzofuran building block was prepared through a domino Sonogashira coupling/5-endo-dig cyclization and converted into a stable 1-hydroxybenzotriazole-derived active ester prior to linking with a galactosylated hydroxyacetophenone unit. The elaborated synthesis requires only nine steps (11 % overall yield) along the longest linear sequence and paves the way for the preparation of structurally related compounds for further biological evaluation.
- Kerl, Thomas,Berger, Florian,Schmalz, Hans-Günther
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p. 2935 - 2938
(2016/03/25)
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- A catechin preparation method of compound (by machine translation)
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The invention relates to a method for preparing a catechin compound. The method comprises the following steps: by taking 2,4,6-trihydroxy acetophenone and p-hydroxy benzaldehyde as raw materials, carrying out condensation reaction, restored deoxidation, cyclization reaction of acid catalysis, so as to obtain the catechin compound. The invention also provides a technology for producing the catechin compound. In the synthesis process of an immediate 9, reduction is carried out by using sodium borohydride which is catalyzed by a lewis acid, so that side reaction caused by double bond transfer is greatly reduced while a highly toxic reagent osmium tetroxide is replaced with hydrogen peroxide oxidation.
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Paragraph 0029; 0030
(2017/02/23)
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- NOVEL ANALOGUES OF EPICATECHIN AND RELATED POLYPHENOLS
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The present invention provides novel analogues of epicatechin and related polyphenols, their variously functionalized derivatives, process for preparation of the same, composition comprising these compounds and their method of use.
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Paragraph 01219; 0220
(2016/03/05)
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- NEW C-GLYCOSYLPOLYPHENOL ANTIDIABETIC AGENTS, EFFECT ON GLUCOSE TOLERANCE AND INTERACTION WITH BETA-AMYLOID. THERAPEUTIC APPLICATIONS OF THE SYNTHESIZED AGENT(S) AND OF GENISTA TENERA ETHYL ACETATE EXTRACTS CONTAINING SOME OF THOSE AGENTS
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The present invention concerns the antidiabetic-activity of compounds type A, namely of 8-β-D-glucosylgenistein, which is not toxic to eukaryotic cells and has demonstrated to produce complete normalization of fasting hyperglycaemia, to reduce excessive p
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Page/Page column 0079; 0080; 0081
(2015/02/19)
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- ANTIBACTERIAL AGENT
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An antibacterial agent comprising a compound represented by the following general formula (I), which can exhibit potent antibacterial activity against bacteria that have acquired resistance to quinolones (in the formula, R1 and R4 re
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Paragraph 0132; 0133
(2015/11/30)
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- Neochromine S5 improves contact hypersensitivity through a selective effect on activated T lymphocytes
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Strategy on activated T cells is an effective treatment for T cell mediated diseases. By using a synthesized chromone derivative, we examined its effects on the activated T cells. This compound, (Z)-1,3-dihydroxy-9-methyl-13H-benzo[b]chromeno[3,2-f][1,4]oxazepin-13-one (neochromine S5), exhibited immunosuppressive activity in vitro and in vivo. Interestingly, neochromine S5 selectively inhibited proliferation and induced apoptosis in T lymphocytes activated by concanavalin A (Con A) in a dose-dependent manner but not in nave T lymphocytes, distinct from quercetin. This compound triggered mitochondrial apoptotic pathway including cleavage of caspase 3, caspase 9 and PARP, downregulation of bcl-2 and release of cytochrome c in activated T cells, but did not affect ER stress or Fas signals. In addition, neochromine S5 downregulated the expression of CD25 and CD69 and the production of inflammatory cytokines, including TNFα, IFNγ and IL-2, improved ear swelling in mice with contact hypersensitivity, reduced CD4+ T cells infiltration, and increased apoptosis of isolated T lymphocytes from peripheral lymph nodes. Moreover, neochromine S5 showed no effect on the weight of mice and their immune organs, while dexamethasone caused a significant weight loss. Taken together, our results suggest that neochromine S5 exerts a unique anti-inflammatory activity mainly through a selective effect on activated T cells, which is different from the current immunosuppressant, dexamethasone.
- Gao, Zhe,Ma, Yuxiang,Zhao, Dan,Zhang, Xiong,Zhou, Hang,Liu, Hailiang,Zhou, Yang,Wu, Xuefeng,Shen, Yan,Sun, Yang,Li, Jianxin,Wu, Xudong,Xu, Qiang
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p. 358 - 368
(2015/02/19)
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- Total synthesis of icaritin via microwave-assistance Claisen rearrangement
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The novel total synthesis of icaritin (1), naturally occurring with important bioactive 8-prenylflavonoid, was performed via a reaction sequence of 8 steps including Baker-Venkataraman reaction, chemoselective benzyl or methoxymethyl protection, dimethyldioxirane (DMDO) oxidation, O-prenylation, Claisen rearrangement and deprotection, starting from 2,4,6-trihydroxyacetophenone and 4-hydroxybenzoic acid in overall yields of 23%. The key step was Claisen rearrangement under microwave irradiation. MS, 1H and 13C NMR techniques have been used to confirm the structures of all synthetic compounds.
- Nguyen, Van-Son,Shi, Ling,Li, Yue,Wang, Qiu-An
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supporting information
p. 677 - 681
(2015/04/14)
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- Exploiting the therapeutic potential of 8-β- d -glucopyranosylgenistein: Synthesis, antidiabetic activity, and molecular interaction with islet amyloid polypeptide and amyloid β-peptide (1-42)
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8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of exce
- Jesus, Ana R.,Dias, Catarina,Matos, Ana M.,De Almeida, Rodrigo F.M.,Viana, Ana S.,Marcelo, Filipa,Ribeiro, Rogério T.,Macedo, Maria P.,Airoldi, Cristina,Nicotra, Francesco,Martins, Alice,Cabrita, Eurico J.,Jiménez-Barbero, Jesús,Rauter, Amélia P.
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p. 9463 - 9472
(2015/02/02)
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- Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90 inhibitors
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(-)-Epigallocatechin gallate (EGCG) is the major flavonoid of green tea and has been widely explored for a range of biological activities including anti-infective, anti-inflammatory, anti-cancer, and neuroprotection. Existing structure-activity data for EGCG has been largely limited to exploration of simple ethers and hydroxyl deletion. EGCG has poor drug-like properties because of multiple phenolic hydroxyl moieties and a metabolically labile ester. This work reports a substantial expansion of structure-activity understanding by exploring a range of semi-synthetic and synthetic derivatives with ester replacements and variously substituted aromatic and alicyclic groups containing more drug-like substituents. Structure-activity relationships for these molecules were obtained for Hsp90 inhibition. The results indicate that amide and sulfonamide linkers are suitable ester replacements. Hydroxylated aromatic rings and the cis-stereochemistry in EGCG are not essential for Hsp90 inhibition. Selected analogs in this series are more potent than EGCG in a luciferase refolding assay for Hsp90 activity.
- Bhat, Rohit,Adam, Amna T.,Lee, Jungeun Jasmine,Gasiewicz, Thomas A.,Henry, Ellen C.,Rotella, David P.
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p. 2263 - 2266
(2014/05/20)
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- Enantioselective synthesis of orthogonally protected (2R,3R)-(-)- epicatechin derivatives, key intermediates in the de novo chemical synthesis of (-)-epicatechin glucuronides and sulfates
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Ten orthogonally protected (-)-epicatechin and 3′- or 4′-O-methyl-(-)-epicatechin derivatives were prepared in a regiospecific and enantioselective manner. For each orthogonally protected (-)-epicatechin derivative, one specific phenolic hydroxyl was protected with a methoxymethyl (MOM) or p-methoxybenyzl (PMB) group and the remainder were protected as benzyl ethers. These uniquely protected (-)-epicatechin derivatives were designed to facilitate the regiospecific installation of a glucuronic acid or sulfate unit onto (-)-epicatechin after selective removal of the MOM or PMB protecting group to provide authentic standards of (-)-epicatechin glucuronides and sulfates.
- Zhang, Mingbao,Erik Jagdmann Jr.,Van Zandt, Michael,Beckett, Paul,Schroeter, Hagen
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p. 362 - 373
(2013/06/27)
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- Design, synthesis and antiviral activity of 2-(3-amino-4-piperazinylphenyl) chromone derivatives
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Previously, we have confirmed that the antiviral activities of the chromone derivatives were controlled by the type as well as the position of the substituents attached to the chromone core structure. In the course of our ongoing efforts to optimize the antiviral activity of the chromone derivatives, we have been attempting to derivatize the chromone scaffold via introduction of various substituents. In this proof-of-concept study, we introduced a 3-amino-4-piperazinylphenyl functionality to the chromone scaffold and evaluated the antiviral activities of the resulting chromone derivatives. The synthesized 2-(3-amino-4-piperazinylphenyl)- chromones showed severe acute respiratory syndrome-corona virus (SARS-CoV)-specific antiviral activity. In particular, the 2-pyridinylpiperazinylphenyl substituents provided the resulting chromone derivatives with selective antiviral activity. Taken together, this result indicates the possible pharmacophoric role of the 2-pyridinylpiperazine functionality attached to the chromone scaffold, which warrants further in-depth structure-activity relationship study.
- Kim, Mi Kyoung,Yoon, Hyunjun,Barnard, Dale Lynn,Chong, Youhoon
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p. 486 - 488
(2013/05/22)
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- Study of kaempferol glycoside as an insulin mimic reveals glycon to be the key active structure
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Diabetes mellitus is increasing in prevalence with patient numbers rising throughout the world. Current treatments for diabetes mellitus focus on control of blood glucose levels. Certain kinds of flavonoids or their glycosides stimulate cells to improve glucose uptake and lower blood glucose levels. We synthesized kaempferol 3-O-neohesperidoside (1), a naturally occurring substance present in Cyathea phalerata Mart., reported to mimic the action of insulin. Synthetic 1 promoted glucose uptake in the cultured cell line, L6. Further studies to determine the core structure responsible for this activity using synthetic compounds revealed neohesperidose to be the primary pharmacophore. These findings support the use of certain saccharides as a potential novel treatment for diabetes mellitus by replacing or supporting insulin.
- Yamasaki, Kazuaki,Hishiki, Ryogo,Kato, Eisuke,Kawabata, Jun
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supporting information; experimental part
p. 17 - 21
(2011/04/17)
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- Total synthesis of 3′,3?-binaringenin and related biflavonoids
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The synthesis of natural 3++,3?-binaringenin and four related biflavonoids was performed in good overall yield (15-35%) starting from readily available phloroglucinol and 4-hydroxy- or 4-methoxybenzaldehyde. Preliminary results indicate that some of these compounds have an interesting activity against S. aureus. Georg Thieme Verlag Stuttgart.
- Sagrera, Gabriel,Seoane, Gustavo
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scheme or table
p. 2776 - 2786
(2010/10/19)
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- Synthesis of a novel series of diphenolic chromone derivatives as inhibitors of NO production in LPS-activated RAW264.7 macrophages
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A novel series of diphenolic chromone derivatives were synthesized and their inhibitory activity on nitric oxide (NO) production and cytotoxicity were evaluated using LPS-activated murine macrophages RAW264.7 assay and MTT method, respectively. Among these compounds, (5,7-dihydroxy-4-oxo-4H-chromen-3-yl) methyl esters (6b, 6c, 6f, 6g, and 6h) showed quite potent inhibitory activities with IC50 values of 2.20, 3.48, 0.35, 0.80, and 0.61 μM, respectively. The MTT results showed that all of the active compounds exhibited no cytotoxicity at the effective concentrations. The preliminary mechanism of the most potent compounds (6b, 6c, 6f, 6g, and 6h) was further examined based on the RT-PCR results and the compounds 6f, 6g, and 6h inhibited NO production by suppressing the expression of iNOS mRNA in a dose dependent manner. Furthermore, a computational analysis of physicochemical parameters revealed that the most of the compounds possessed drug-like properties.
- Liu, Guo-Biao,Xu, Jian-Liang,Geng, Mei,Xu, Rui,Hui, Rong-Rong,Zhao, Jian-Wei,Xu, Qiang,Xu, Hong-Xi,Li, Jian-Xin
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experimental part
p. 2864 - 2871
(2010/07/04)
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- C-Glucosylflavonoid biosynthesis from 2-hydroxynaringenin by Desmodium uncinatum (Jacq.) (Fabaceae)
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[2′,3′,5′,6′-2H4]-2-Hydroxynaringenin is synthesised and incubated with commercially available UDP-glucose and the crude protein extract from Desmoduim uncinatum leaves. The organic extract produces isotopically labelled [2′,3′,5′,6′-2H4]-vitexin and [2′,3′,5′,6′-2H4]-isovitexin. Repeating the experiment with denatured protein or replacing the 2-hydroxynaringenin with [2′,3′,5′,6′-2H4]-apigenin or [2′,3′,5′,6′-2H4]-naringenin results in no observable incorporation. 2-Hydroxynaringenin is therefore the substrate for C-glucosylflavonoid biosynthesis in D. uncinatum.
- Hamilton, Mary L.,Caulfield, John C.,Pickett, John A.,Hooper, Antony M.
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scheme or table
p. 5656 - 5659
(2011/02/24)
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- PREPARATION OF (+)-CATECHIN, (-)-EPICATECHIN, (-)-CATECHIN, (+)-EPICATECHIN, AND THEIR 5,7,3',4'-TETRA-O-BENZYL ANALOGUES
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Processes for preparing racemic mixtures of 5,7,3',4'-tetra-O-benzyl-(±)-catechin and (±)-epicatechin involves (i) condensing 2-hydroxy-4,6-bis(benzyloxy)-acetophenone and 3,4-bis(benzyloxy)benzaldehyde, cyclizing the resulting compound, oxidizing the resulting compound; (ii) dihydroxylating (E)-3-(3',4'-bis(benzyloxy)phenyl)prop-2-ene-1 -ol and reducing the 1 ,2-diol; or (iii) coupling 3,5-bis(benzyloxy)phenol with (£)-3,5-bis(benzyloxy)-2-(3',4'-bis(benzyloxy)phenyl)allyl)phenol and cyclizing the resulting chalcone. A process for preparing the benzylated epimers of catechin and epicatechin involves seven steps. 3,4-Bis(benzyloxy)benzaldehyde is coupled with 2-hydroxy-4,6-benzyloxy-acetophenone to form a chalcone. The chalcone is selectively reduced to an alkene. The phenolic group of the alkene is protected. The protected alkene is asymetrically dihydroxylated. The resulting compound is deprotected, cyclized, and finally hydrolyzed. Epimers resulting from these processes are chemically resolved or separated by chiral high pressure liquid chromatography. Also disclosed is a method for preparing enantiomerically pure 5,7,3',4'-tetra-O-benzyl-(+)-catechin from a racemic mixture using dibenzoyl-L-tartaric acid monomethyl ester. Further, disclosed is an improved process for preparing dibenzoyl-L-tartaric acid monomethyl ester.
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Page/Page column 7; 21-23
(2010/11/25)
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- Isotopic labelling of quercetin 3-glucoside
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The potentially important dietary antioxidant, quercetin 3-O-β-d-glucoside, has been 13C-labelled at C-2 of the flavonoid unit by synthesis in 15% yield over five steps from [13C]carbon dioxide. The route is appropriate for radiochemical synthesis. Formation of the protected 3-glucosylated flavonol appears to result from [1,7]-sigmatropic rearrangement with migration of a benzyl group followed by cyclisation. A free 5-OH results even when a phosphazene superbase is used.
- Caldwell, Stuart T.,Petersson, Hanna M.,Farrugia, Louis J.,Mullen, William,Crozier, Alan,Hartley, Richard C.
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p. 7257 - 7265
(2007/10/03)
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- Structural studies on bioactive compounds. 40.1 synthesis and biological properties of fluoro-, methoxyl-, and amino-substituted 3-phenyl-4H-1-benzopyran-4-ones and a comparison of their antitumor activities with the activities of related 2-phenylbenzothiazoles
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A new series of fluoro-, methoxyl-, and amino-substituted isoflavones have been synthesized as potential antitumor agents based on structural similarities to known flavones and isoflavones (quercetin and genistein respectively) and antitumor 2-phenylbenzothiazoles. Target compounds were synthesized using palladium-catalyzed coupling methodologies to construct the central aryl carbon-carbon single bond. The new isoflavone derivatives were tested for in vitro activity in human breast (MDA-MB-468 and MCF-7) and colon (HT29 and HCT-116) cancer cell lines. Low micromolar GI50 values were obtained in a number of cases, with the MDA-MB-468 cell line being the most sensitive overall. Notably, significant potentiation of growth inhibitory activity (GI50 1 μM for 12d, 12f, 12h, 12k, 121, 12o but not the methylene-bridged derivative 12i) was observed when MDA-MB-468 cells were co-incubated with TBDD, a powerful inducer of cytochrome P450 (CYP)-1A1 activity, suggesting that isoflavone derivatives can act as substrates for CYP1A1 bioactivation.
- Vasselin, David A.,Westwell, Andrew D.,Matthews, Charles S.,Bradshaw, Tracey D.,Stevens, Malcolm F. G.
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p. 3973 - 3981
(2007/10/03)
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- FUSED HETEROCYCLIC DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, AND MEDICINAL USE THEREOF
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The present invention provides fused heterocyclic derivatives represented by the general formula: wherein R1 represents H, halogen, OH, etc.; R2 represents H, halogen or an alkyl group; R3 and R4 represent H, OH, halogen, etc.; Q represents alkylene, etc.; ring A represents aryl or heteroaryl; and G represents or ???or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, pharmaceutical compositions comprising the same, and pharmaceutical uses thereof.
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Page/Page column 41-42
(2008/06/13)
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- Analogs of green tea polyphenols as chemotherapeutic and chemopreventive agents
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Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of polyphenol catechins that occur in green tea, such as epigallocatichin-3-gallate (EGCG), and have the structure of formula (I) wherein R1 through R11 are defined herein. Preferred R4 moieties are selected from O, S, NH and CH2, and in exemplary compounds, R4 is O and R5 is a tri-substituted aroyloxy substituent, such as a 3,4,5-substituted benzoyloxy group. Pharmaceutical compositions are provided as well, as are methods of chemotherapy and chemoprevention.
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- Novel flavanoids as chemotherapeutic, chemopreventive, and antiangiogenic agents
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Novel compounds are useful as chemotherapeutic, chemopreventative, and antiangiogenic agents are provided. The compounds are flavanoids, including flavanones, flavanols, and chalcones. The compounds have the structure of formula (I) 1wherein R1 through R3 and R5 through R11 are defined herein, and α, β, and γ are optional bonds, providing that when α is absent, β is present, and when β is absent, α is present. When α is present, preferred R4 moieties are selected from O, S, NH and CH2, and when α is absent, preferred R4 groups are selected from OH, SH, NH2 and CH3. When γ is present, the preferred R5 substituent is O, while when γ is absent, the preferred R5 substituent is OH. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.
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- Analogs of green tea polyphenols as chemotherapeutic and chemopreventive agents
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Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of polyphenol catechins that occur in green tea, such as epigallocatichin-3-gallate (EGCG), and have the structure of formula (I) wherein R1 through R11 are defined herein. Preferred R4 moieties are selected from O, S, NH and CH2, and in exemplary compounds, R4 is O and R5 is a tri-substituted aroyloxy substituent, such as a 3,4,5-substituted benzoyloxy group. Pharmaceutical compositions are provided as well, as are methods of chemotherapy and chemoprevention.
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- Novel flavanoids as chemotherapeutic, chemopreventive, and antiangiogenic agents
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Novel compounds useful as chemotherapeutic, chemopreventive, and antiangiogenic agents are provided. The compounds are flavanoids, including flavanones, flavanols, and chalcones. The compounds have the structure of formula (I) wherein R1 through R3 and R5 through R11 are defined herein, and α, β and γ are optional bonds, providing that when α is absent, β is present, and when β is absent, α is present. When α is present, preferred R4 moieties are selected from O, S, NH and CH2, and when α is absent, preferred R4 groups are selected from OH, SH, NH2 and CH3. When γ is present, the preferred R5 substituent is O, while when γ is absent, the preferred R5 substituent is OH. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.
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- Synthesis of 8-C-glucosylflavones
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The syntheses of orientin, parkinsonin A, isoswertiajaponin, and parkinsonin B, which are 8-C-β-D-glucopyranosyl-3′,4′,5,7-tetrahydroxyflavone, 5-methyl orientin, 7-methyl orientin, and 5,7-dimethyl orientin, respectively, are reported herein. The C-glucosyl phloroacetophenone derivatives were obtained via a regio- and stereoselective O → C glycosyl rearrangement. Aldol condensation of the C-glucosyl phloroacetophenone derivatives with 3,4-bisbenzyloxybenzaldehyde afforded the corresponding C-glucosylchalcones. Construction of the flavone system by reaction with I2-Me2SO, followed by the elimination of the 5-benzyl protecting group in the flavone structure, yielded an orientin derivative and a isoswertiajaponin derivative. Methylation of the orientin derivatives with dimethyl sulfate afforded the parkinsonin A derivative, the isoswertiajaponin derivative, and the parkinsonin B derivative. Finally, hydrogenolysis of these C-glucosylflavone derivatives led to the four 8-C-glucosylflavones. The NMR spectra of these C-glucosylflavones showed a duplication of signals corresponding to a major rotamer, along with a minor one. Based on NOESY experiments in Me2SO at ambient temperature, they adopted conformations in which the H-2″ and H-4″ protons in the glucose moiety were oriented toward the B-ring in the flavone structure.
- Kumazawa,Kimura,Matsuba,Sato,Onodera
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p. 183 - 193
(2007/10/03)
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- Simplified catechin-gallate inhibitors of HIV-1 reverse transcriptase
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Systematic simplification of the molecular structures of epicatechin gallate and epigallocatechin gallate to determine the minimum structural characteristics necessary for HIV-1 reverse transcriptase inhibition in vitro resulted in several compounds that strongly inhibited the native as well as the A17 double mutant (K103N Y181C) enzyme, which is normally insensitive to most known nonnucleoside inhibitors.
- Tillekeratne,Sherette,Grossman,Hupe,Hupe,Hudson
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p. 2763 - 2767
(2007/10/03)
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- Synthesis of a 3,4,5-trimethoxybenzoyl ester analogue of epigallocatechin-3-gallate (EGCG): A potential route to the natural product green tea catechin, EGCG
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matrix presented The synthesis of a trimethoxybenzoyl ester (D-ring) analogue of epigallocatechin-3-gallate (EGCG) is described. The versatile synthesis route can be used to synthesize A, B, and D ring analogues of EGCG and involves a key cyclization of t
- Zaveri, Nurulain T.
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p. 843 - 845
(2007/10/03)
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- Facile total syntheses of two novel 4-alkenyloxy-2,6- dihydroxyacetophenones
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Two novel acetophenones, 4-(1'-geranyloxy)-2,6-dihydroxyacetophenone 1 and 4-(1'-farnesyloxy)-2,6-dihydroxyacetophenone 2 isolated from the fruit of Evodia merrillii and from the aerial parts of Borronia ramosa respectively, have been synthesized starting from 2,4,6-trihydroxyacetophenone 3; the key step in their total synthesis is the regioselective alkenylation onto the intermediate 6 with alkenyl bromide.
- Huang, Chusheng,Zhang, Zhe,Li, Shuhua,Li, Yulin
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p. 148 - 149
(2007/10/03)
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- Total synthesis of 8-(1,1-dimethylallyl)-apigenin
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8-(1,1-Dimethylallyl)apigenin has been synthesized in 5 steps from 2′, 4′-dibenzylphloroacetophenone and 4-O-methoxyethoxymethylbenzaldehyde. The strategy involved protection of the 4′-hydroxyl in apigenin by a methoxyethoxymethyl group, followed by specific O-prenylation at position 7. Claisen rearrangement of the 7-prenyl-4′-methoxyethoxymethylapigenin performed in one step both the 1,1-dimethylallylation at position 8, and removal of the 4′-methoxyethoxymethyl protecting group.
- Raguenet, Helene,Barron, Denis,Mariotte, Anne-Marie
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p. 277 - 285
(2007/10/03)
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- Synthesis of Pyranoisoflavones from Pyronochalcones: Synthesis of Elongatin and Its Angular Isomer
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Elongatin (4',5-dihydroxy-2',5'-dimethoxy-2'',2''-dimethylpyranoisoflavone) was synthesized by an oxidative rearrangement of the corresponding pyronochalcone with thallium(III) nitrate and a regioselective reduction of 7-(4-benzoyloxy-2,5-dimethoxyphenyl)-2,3-dihydro-2,2-dimethyl-5-tosyloxy-4H,6H-benzodipyran-4,6-dione with sodium borohydride-palladium chloride, followed by dehydration of the resultant alcohol and hydrolysis.Its angular isomer (4',5-dihydroxy-2',5'-dimethoxy-2'',2''-dimethylpyranoisoflavone) was also synthesized from the corresponding pyronochalcone in a similar manner.
- Tsukayama, Masao,Kawamura, Yasuhiko,Tamaki, Hiroto,Kubo, Tomoya,Horie, Tokunaru
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p. 826 - 832
(2007/10/02)
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- Synthesis of Naturally Occuring Pratensein and 6,8-Di-C-prenylpratensein
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Pratensein (4a) has now been synthesized in two ways.The first route involves condensation of phloroacetophenone dibenzyl ether (1) with O-benzylisovanillin (2) and oxidative cyclization of the resulting chalcone (3) with Tl(NO3)3-MeOH followed by boiling with HCl.In the second route 2,4,6,3'-tetrahydroxy-4'-methoxydesoxybenzoin (5) is treated with DMF, CH3SO2Cl and BF3-Et2O.When pratensein is reacted with 3-hydroxy-3-methyl-1-butene in the presence of BF3-Et2O and dioxan, it gives the naturally occuring 6,8-di-C-prenylpratensein (6a).
- Jain, A. C.,Bambah, P. K.
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p. 488 - 490
(2007/10/02)
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- Synthesis of Licoisoflavone A and Related Compounds
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2',4',5,7-Tetrahydroxyisoflavone was partially benzoylated with benzoyl chloride to give 7-benzoyloxy-2',4',5-trihydroxyisoflavone.The condensation of the 7-(benzoyloxy)isoflavone with 2-methyl-3-buten-2-ol, followed by the hydrolysis of the resultant 3'-(3-methyl-2-butenyl)isoflavone gave licoisoflavone A.Its 5'-(3-methyl-2-butenyl) isomer was also synthesized from 5-benzoyloxy-2',4',7-trihydroxyisoflavone in a similar manner.
- Tsukayma, Masao,Fujimoto, Kunihiro,Horie, Tokunaru,Masumura, Mitsuo,Nakayama, Mitsuru
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p. 136 - 141
(2007/10/02)
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- β-Ketocarboxyl and phosphonate dihydro-chalcone sweeteners
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Dihydrochalcones of the formula STR1 are disclosed wherein M+ is a physiologically acceptable cation, X is H or OH, R is a lower alkyl and R' is STR2 and n and q, respectively, may have a numerical value of 1 to 6. These materials are useful as sweeteners for edibles.
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- Total Synthesis of Junipegenin-A, an Isoflavone from Juniperus macropoda
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Junipegenin-A (1), a new isoflavone isolated from Juniperus macropoda has been synthesised in nine steps, starting from gallic acid.The key step is the oxidative rearrangement of the intermediate benzyloxychalkone (9) by thallium(III) nitrate to give acetal (10) followed by cyclisation to the corresponding isoflavone (1), identical (m.m.p., co-TLC and co-IR) with a natural sample.
- Sethi, M. L.,Taneja, S. C.,Dhar, K. L.,Atal, C. K.
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p. 770 - 772
(2007/10/02)
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- Comestibles sweetened with alpha amino acid dihydrochalcones
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Dihydrochalcones of the formula STR1 are disclosed wherein X is H or OH and R is a lower alkyl. These materials are useful as sweeteners for edibles. A process for preparing these compounds using a novel intermediate is disclosed as are acid and base neutralization products of the subject dihydrochalcones.
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- Flavonone precursors for alpha amino acid dihydrochalcones
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Dihydrochalcones of the formula STR1 are disclosed wherein X is H or OH and R is a lower alkyl. These materials are useful as sweeteners for edibles. A process for preparing these compounds using a novel intermediate is disclosed as are acid and base neutralization products of the subject dihydrochalcones.
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- Alpha amino acid dihydrochalcones
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Dihydrochalcones of the formula STR1 are disclosed wherein X is H or OH and R is lower alkyl. These materials are useful as sweeteners for edibles. A process for preparing these compounds using a novel intermediate is disclosed as are acid and base neutralization products of the subject dihydrochalcones.
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