- Dihydroactinidiolide, a natural product against Aβ25-35 induced toxicity in Neuro2a cells: Synthesis, in silico and in vitro studies
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Synthesis of natural products has speeded up drug discovery process by minimizing the time for their purification from natural source. Several diseases like Alzheimer's disease (AD) demand exploring multi targeted drug candidates, and for the first time we report the multi AD target inhibitory potential of synthesized dihydroactinidiolide (DA). Though the activity of DA in several solvent extracts have been proved to possess free radical scavenging, anti bacterial and anti cancer activities, its neuroprotective efficacy has not been evidenced yet. Hence DA was successfully synthesized from β-ionone using facile two-step oxidation method. It showed potent acetylcholinesterase (AChE) inhibition with half maximal inhibitory concentration (IC50) 34.03 nM, which was further supported by molecular docking results showing strong H bonding with some of the active site residues such as GLY117, GLY119 and SER200 of AChE. Further it displayed DPPH and (.NO) scavenging activity with IC50 value 50 nM and metal chelating activity with IC50 >270 nM. Besides, it significantly prevented amyloid β25-35 self-aggregation and promoted its disaggregation at 270 nM. It did not show cytotoxic effect towards Neuro2a (N2a) cells up to 24 h at 50 and 270 nM while it significantly increased viability of amyloid β25-35 treated N2a cells through ROS generation at both the concentrations. Cytotoxicity profile of DA against human PBMC was quite impressive. Hemolysis studies also revealed very low hemolysis i.e. minimum 2.35 to maximum 5.61%. It also had suitable ADME properties which proved its druglikeness. The current findings demand for further in vitro and in vivo studies to develop DA as a multi target lead against AD.
- Das, Mamali,Prakash, Sengodu,Nayak, Chirasmita,Thangavel, Nandhini,Singh, Sanjeev Kumar,Manisankar, Paramasivam,Devi, Kasi Pandima
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p. 340 - 349
(2018/09/10)
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- β-Carotene autoxidation: Oxygen copolymerization, non-vitamin A products, and immunological activity
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Carotenoids are reported to have immunological effects independent of vitamin A activity. Although antioxidant activity has been suggested as a basis of action, the ability of carotenoids to autoxidize to numerous non-vitamin A products with immunological activity is an alternative yet to be fully explored. We have undertaken a systematic study of β-carotene autoxidation and tested the product mixture for immunological activity. Autoxidation proceeds predominantly by oxygen copolymerization, leading to a defined, reproducible product corresponding to net uptake of almost 8 molar equivalents of oxygen. The product, termed OxC-beta, empirical formula C40H60O 15 versus C40H56 for β-carotene, contains more than 30% oxygen (w/w) and 85% β-carotene oxygen copolymers (w/w) as well as minor amounts of many C8-C18 norisoprenoid compounds. No vitamin A or higher molecular weight norisoprenoids are present. The predominance of polymeric products has not been reported previously. The polymer appears to be a less polymerized form of sporopollenin, a biopolymer found in exines of spores and pollen. Autoxidations of lycopene and canthaxanthin show a similar predominance of polymeric products. OxC-beta exhibits immunological activity in a PCR gene expression array, indicating that carotenoid oxidation produces non-vitamin A products with immunomodulatory potential.
- Burton, Graham W.,Daroszewski, Janusz,Nickerson, James G.,Johnston, James B.,Mogg, Trevor J.,Nikiforov, Grigory B.
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supporting information
p. 305 - 316
(2014/05/06)
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- Cu(I)-catalyzed oxidative cyclization of alkynyl oxiranes and oxetanes
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In the presence of a Cu(I) catalyst and a pyridine oxide, alkynyl oxiranes and oxetanes can be converted into functionalized five- or six-membered α,β-unsaturated lactones or dihydrofuranaldehydes. This new oxidative cyclization is proposed to proceed via an unusual allenyloxypyridinium intermediate.
- Gronnier, Colombe,Kramer, Soren,Odabachian, Yann,Gagosz, Fabien
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p. 828 - 831
(2012/03/07)
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- Total synthesis of (±)-dihydroactinidiolide using selenium-stabilized carbenium ion
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A new, short total synthesis of dihydroactinidiolide 1 is described using selenium carbenium ion-promoted carbon-carbon bond formation as the key step. Our synthetic strategy starts with a lactonization reaction between 1,3,3-trimethylcyclohexene 13 and α-chloro-α-phenylseleno ethyl acetate 14, affording the key intermediate, α-phenylseleno-γ-butyro lactone 15, which reacted via a selenoxide elimination to the target compound 1.
- Dabdoub, Miguel J.,Silveira, Claudio C.,Lenard?o, Eder J.,Guerrero Jr., Palimécio G.,Viana, Luiz H.,Kawasoko, Cristiane Y.,Baroni, Adriano C.M.
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scheme or table
p. 5569 - 5571
(2011/02/24)
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- Generation of norisoprenoid flavors from carotenoids by fungal peroxidases
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To biotechnologlcally produce norisoprenoid flavor compounds, two extracellular peroxidases (MsP1 and MsP2) capable of degrading carotenoids were isolated from the culture supematants of the basidiomycete Marasmlus scorodonlus (garlic mushroom). The encod
- Zelena, Kateryna,Hardebusch, Bjoern,Huelsdau, Baerbel,Berger, Ralf G.,Zorn, Holger
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experimental part
p. 9951 - 9955
(2010/07/18)
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- Synthesis of loliolide, actinidiolide, dihydroactinidiolide, and aeginetolide via cerium enolate chemistry
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(Chemical Equation Presented) Loliolide, aeginetolide, actinidiolide, and dihydroactinidiolide were synthesized in racemic form from a single common intermediate, prepared through the 1,2 addition of the cerium enolate of ethyl acetate to 2,6,6-trimethylcylohexenone.
- Eidman, Kirk F.,MacDougall, Brian S.
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p. 9513 - 9516
(2007/10/03)
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- Effect of cis/trans isomerism of β-carotene on the ratios of volatile compounds produced during oxidative degradation
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β-Carotene is, when cleaved, an important source of flavor and aroma compounds in fruits and flowers. Among these aroma compounds, the main degradation products are β-ionone, 5,6-epoxy-β-ionone, and dihydroactinidiolide (DHA), which are associated by flavorists and perfumers with fruity, floral, and woody notes. These three species can be produced by degradation of β-carotene through an attack by enzyme-generated free radicals and a cleavage at the C9-C10 bond. This study investigated the influence of cis/trans isomerism at the C9-C10 bond on the production of β-carotene degradation compounds, first with a predictive approach and then experimentally with different isomer mixtures. β-Carotene solutions containing high ratios of 9-cis-isomers produced more DHA, suggesting a different pathway than for the transformation of all-trans-β-carotene to ionone and DHA. These results are important in the search for financially viable processes to produce natural carotene-derived aroma compounds.
- Wache, Yves,Bosser-DeRatuld, Aurelie,Lhuguenot, Jean-Claude,Belin, Jean-Marc
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p. 1984 - 1987
(2007/10/03)
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- Total Synthesis of (R)-Dihydroactinidiolide and (R)-Actinidiolide Using Asymmetric Catalytic Hetero-Diels-Alder Methodology
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The total synthesis of the naturally occurring bicyclic lactones (R)-dihydroactinidiolide and (R)-actinidiolide is presented. The key step in the syntheses is the copper(II)-bisoxazoline-catalyzed hetero-Diels-Alder reaction of a cyclic diene with ethyl glyoxylate giving the hetero-Diels-Alder product in high yield and with very high regio-, diastereo-, and enantioselectivity. The total syntheses proceed via an intermediate, which also has the potential for a series of other natural products. The structure of the key intermediate is confirmed by X-ray analysis.
- Yao, Sulan,Johannsen, Mogens,Hazell, Rita G.,J?rgensen, Karl Anker
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p. 118 - 121
(2007/10/03)
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- Convenient Synthesis of 2,2-Diethoxy-2,5-dihydrofurans, 2(5H)Furanones and 2-Ethoxyfurans. Crystal and Molecular Structure of a Barrelenone Diels-Alder Product
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Reaction of 1,2-hydroxyketones 5 with (2,2-diethoxyvinylidene)triphenylphosphorane (2) or (2,2-diethoxyvinyl)triphenylphosphonium tetrafluoroborates 6 yields the 2,2-diethoxy-2,5-dihydrofurans 9.Depending on the reaction conditions used, the orthoesters 9 can be hydrolized to give 2(5H)furanones 10 and 2-ethoxyfurans 11, respectively. 4,5-Dimethyl-5,6-dihydro-2-pyranone (20) and 8-methoxycoumarin (23) are prepared, starting from (2,2-diethoxyvinyl)triphenylphosphonium tetrafluoroborate (6a) and 1-hydroxy-2-methyl-3-butanone (16) or 2-hydroxy-3-methoxy-benzaldehyde (21).The 2-ethoxyfuranes 11 readily undergo Diels-Alder reactions with 2-chloracrylonitrile (24), maleic anhydride (26), N-phenyl-1,2,4-triazoline-3,5-dione (28) and dimethyl acetylenedicarboxylate (30) to give the corresponding Diels-Alder products 25, 27, 29 and 31, respectively.Contrary to 2-ethoxyfuran 11b, 11a reacts with two equivalents of acetylene 30, to yield barrelenone 34.The structure of 34 unequivocally is established by X-ray structure analysis. - Keywords: 2,2-Diethoxy-2,5-dihydrofurans, 2(5H)Furanones, 2-Ethoxyfurans, Barrelenone, Diels-Alder Products, X-Ray
- Saalfrank, Rolf W.,Hafner, Wieland,Markmann, Joachim,Welch, Andreas,Peters, Karl,Schnering, Hans Georg von
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p. 389 - 406
(2007/10/02)
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- Oxidative degradation of β-carotene and β-apo-8′-carotenal
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In the self-initiated oxidation of β-carotene with molecular oxygen the rate of oxygen uptake was shown to depend on the oxygen partial pressure. Epoxides, dihydrofurans, carbonyl compounds, carbon dioxide, oligomeric material, traces of alcohols, and probably carboxylic acids were formed. The main products in the early stage of the oxidation were shown to be 5,6-epoxy-β-carotene. 15,15′-epoxy-′-carotene, diepoxides, and a series of β-apo-carotenals and -carotenones. As the oxidation proceeded uncharacterised oligomeric material and the carbonyl compounds became more important and the epoxides degraded. In the final phase of the oxidation the longer chain β-apo-carotenals were themselves oxidized to shorter chain carbonyl compounds, particularly β-apo-13-carotenone, β-ionone, 5,6-epoxy-gb-ionone, dihydroactinidiolide and probably carboxylic acids. The effect of iron, copper and zinc stearates on the product composition and proportions was studied, as was the effect of light. The oxidation was inhibited by 2,6-di-t-butyl-4-methyphenol and α-tocopherol. The oxidations of β-apo-8′-carotenal and retinal under similar conditions were studied briefly, and the main products from the former compound were characterized. The initiation, the formation of the epoxides, the β-apo-carotenals and -carotenones, the successive chain shortening of the aldehydes to the ketones, and the formation of dihydroactinidiolide are explained in terms of free radical peroxidation chemistry.
- Mordi, Raphael C.,Walton, John C.,Burton, Graham W.,Hughes, Lise,Ingold U., Keith,Lindsay A., David,Moffatt J., Douglas
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p. 911 - 928
(2007/10/02)
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- AN IMPROVED SYNTHESIS OF (+/-)-DIHYDROACTINIDIOLIDE
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An improved synthesis of (+/-)-aeginetolide (2) and (+/-)-dihydroactinidiolide (1) from 2,6,6-trimethyl-1-cyclohexene-1-acetaldehyde (4) has been achieved.
- Subbaraju, Gottumukkala V.,Manhas, Maghar S.,Bose, Ajay K.
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p. 4871 - 4874
(2007/10/02)
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- CONVENIENT SYNTHESIS OF 5-ALKYLIDENE-2(5H)-FURANONES, 2(5H)-FURANONES AND 2-ETHOXYFURANS
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Starting from enolizing 1,2-diketones 5 and (2,2-diethoxyvinylidene)triphenylphosphorane (2) or from 5 and (2,2-diethoxyvinyl)triphenylphosphonium tetrafluoroborate (6) the orthoesters 9 are prepared. 9 can be hydrolyzed under acidic conditions to give 5-alkylidene-2(5H)-furanones 10.Reaction of 1,2-hydroxyketones 11 and (2,2-ditehoxyvinylidene)triphenylphosphorane (2) via Michael addition and Wittig reaction yields orthoesters 15, which can be hydrolyzed to give 2(5H)-furanones 16 and 2-ethoxyfurans 17 respectively.A considerable variation of the substitens (R4)can be achieved starting from 11 and (2,2-diethoxyvinyl)triphenylphosphonium tetrafluoroborates 12.
- Saalfrank, R. W.,Hafner, W.,Markmann, J.,Bestmann, H.-J.
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p. 5095 - 5100
(2007/10/02)
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- A HIGHLY EFFICIENT ONE-STEP SYNTHESIS OF (+/-) DIHYDROACTINIDIOLIDE
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An unprecedented reaction of β,γ-unsaturated aldehyde (1) was discovered and has been used to synthesize (+/-) dihydroactinidiolide (2) and (+/-) aeginetolide (3).
- Nickson, Thomas E.
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p. 1433 - 1436
(2007/10/02)
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- SYNTHESIS OF BOTH THE ENANTIOMERS OF DIHYDROACTINIDIOLIDE, A PHEROMONE COMPONENT OF THE RED IMPORTED FIRE ANT
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Both the enantiomers of dihydroactinidiolide (4,4,7a-trimethyl-2-oxo-2,4,5,6,7,7a-hexahydrobenzofuran) were synthesized in 15 steps from (S)-3-hydroxy-2,2-dimethylcyclohexanone
- Mori, Kenji,Nakazono, Yutaka
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p. 283 - 290
(2007/10/02)
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- ASYMMETRIC SYNTHESIS OF (5R,6R)-AEGINETOLIDE AND (5R)-DIHYDROACTINIDIOLIDE FROM (R)-2-HYDROXY-2-METHYLCYCLOHEXANONE
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C11-Cyclic terpenes, (5R,6R)-(-)-aeginetolide and (5R)-(-)-dihydroactinidiolide have been synthesized stereoselectively starting from (R)-2-hydroxy-2-methylcyclohexanone in short steps.
- Sato, Toshio,Funabora, Makoto,Watanabe, Makoto,Fujisawa, Tamotsu
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p. 1391 - 1392
(2007/10/02)
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- A FACILE ENTRY TO BICYCLIC γ-LACTONES AND A SHORT SYNTHESIS OF (+/-)-DIHYDROACTINIDIOLIDE
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A highly useful mode of access to bicyclic γ-lactones 3 from tert-hydroxyolefins 2 with chromium(V) reagent or PCC and its application to the synthesis of (+/-)-dihydroactinidiolide are described.
- Chakraborty, T.K.,Chandrasekaran, S.
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p. 2895 - 2896
(2007/10/02)
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- Fermentation of Fragrances: Biotransformation of β-Ionone by Lasiodiplodia theobromae
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Pre-grown mycelia of Lasiodiplodia theobromae ATCC 28570 transform β-ionone (1) into a large variety of metabolites, by mainly degrading the side-chain of the β-ionone molecule by a C2-unity.The enzyme system responsible for this degradation is proposed to be an oxygenase, which gives rise to the formation of the main product β-cyclo-homogeraniol (8) in analogy to a Baeyer-Villiger oxidation.Further enzymic actions of Lasiodiplodia such as hydrogenations and hydroxylations lead to an accumulation of several not yet described β-ionone metabolites.
- Krasnobajew, Victor,Helmlinger, Daniel
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p. 1590 - 1601
(2007/10/02)
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- Synthesis of (+)-(5S,6S)-Azafrin Methyl Ester; Absolute Configuration of Aeginetic Acid and of Further Vicinal Apocarotene-diols
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We describe the synthesis of a series of optically active vicinal apo-β-carotene-diols.Thus, starting from (+)-(5S,6S)-5,6-dihydroxy-5,6-dihydro-β-ionone (2) we have prepared the (Z/E)-isomeric(+)-C15-esters 7 and 8, the (+)-retinoic derivatives 14, 15, 18, 19 and (+)-methyl azafrinate (22), the enantiomer of the naturally occuring compounds (s.Scheme 1).Our synthesis also establishes the absolute configuration of aeginetic acid (24), aeginetoside (25) and aeginetin (26), compounds isolated from the root parasite Aeginetia indica by Indian and Japanes workers (s.Scheme 2).The presented synthesis of optically active methyl azafrinate confirms our previous assignment of the absolute configuration of azafrin (1a), which was based on degradative evidence.
- Eschenmoser, Walter,Uebelhart, Peter,Eugster, Conrad Hans
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p. 353 - 364
(2007/10/02)
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- Efficient oxidation of β?carotene in μ-carbido diiron octapropyltetraazaporphyrin–tBuOOH system
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The oxidative decomposition of β?carotene mediated by μ-carbido diiron octapropyltetraazaporphyrin ([FeOPrTAP]2C)–tBuOOH system was investigated in benzene. Interaction between tBuOOH and the binuclear complex resulted in the generation of powerful high-oxidized species those are capable of oxidizing the employed substrate within the limits of several minutes. The explanation for such reactivity behavior involves the existence of a mixture of reactive intermediates in the reaction medium: more stable singly oxidized at the macrocyclic ligand π-cation radical as well as much more reactive dication species that is more contributing to the reaction rate. The introduction of imidazole into the coordination sphere of the initial diiron complex accelerates the β?carotene destruction because of generation of a powerful high-oxidizing species, which is capable of oxidizing β?carotene as well as the applied organic peroxide resulting in dioxygen release. Catalytic behavior of all the observed active intermediates was supported by recycling of the reaction under carotene adding. The quantitative characteristics of reactivity of studied systems were obtained and the possible reaction mechanisms were proposed.
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