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New semi-synthetic analogs of oleuropein show improved anticancer activity in?vitro and in?vivo

Oleuropein is a glucosylated seco-iridoid present in olive fruits and leaves. Due to its broad spectrum of biological activities, including anticancer properties, oleuropein has attracted scientific attention for the past 20 years. The promising antiproliferative activity of an olive leaf extract enriched in oleuropein against a series of human cancer cell lines, prompted us to proceed with the semi-synthesis of 51 analogs of oleuropein. Following their initial screening against the estrogen receptor negative breast cancer cell line SKBR3, 7 analogs were shown to display significant cytotoxicity and were further tested against 6 additional solid tumor-derived and leukemic cell lines. The analog with the most promising antitumor activity (24) was selected for more detailed studies. 24 was non-toxic to peripheral blood mononuclear cells derived from healthy blood donors when tested at concentrations close to its half maximal inhibitory concentration. In vivo administration of 24 in melanoma-bearing mice resulted in reducing tumor size in a dose-dependent manner and in inducing anti-melanoma-reactive immune responses. Our results suggest that analog 24, emerging from the initial structure of oleuropein, represents a promising lead structure for further optimization.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

Extracurricular laboratory:new discovery of 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

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Selective C(sp3)?H and C(sp2)?H Fluorination of Alcohols Using Practical Auxiliaries

Selective introduction of fluorine into molecules by the cleavage of inert C?H bonds is of central academic and synthetic interest, yet remains challenging. Given the central role of alcohols in organic chemistry as the most ubiquitous building blocks, a versatile and selective C(sp3)?H and C(sp2)?H fluorination of simple alcohols, enabled by novel designed exo-directing groups, is described. C(sp2)?H bond fluorination was achieved by using a simple acetone oxime as auxiliary, whereas a new, modular and easily accessible bidentate auxiliary was developed for the efficient and site-selective fluorination of various primary methyl, methylene, and benzylic C(sp3)?H bonds. Fluorinated alcohols can readily be accessed by the removal of auxiliaries, and significantly expands the synthetic prospect of the present procedure.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Mechanism of SmI2/amine/H2O-promoted chemoselective reductions of carboxylic acid derivatives (esters, acids, and amides) to alcohols

Samarium(II) iodide-water-amine reagents have emerged as some of the most powerful reagents (E = -2.8 V) for the reduction of unactivated carboxylic acid derivatives to primary alcohols under single electron transfer conditions, a transformation that had been considered to lie outside the scope of the classic SmI2 reductant for more than 30 years. In this article, we present a detailed mechanistic investigation of the reduction of unactivated esters, carboxylic acids, and amides using SmI2-water-amine reagents, in which we compare the reactivity of three functional groups. The mechanism has been studied using the following: (i) kinetic, (ii) reactivity, (iii) radical clock, and (iv) isotopic labeling experiments. The kinetic data indicate that for the three functional groups all reaction components (SmI2, amine, water) are involved in the rate equation and that the rate of electron transfer is facilitated by base assisted deprotonation of water. Notably, the mechanistic details presented herein indicate that complexation between SmI2, water, and amines can result in a new class of structurally diverse, thermodynamically powerful reductants for efficient electron transfer to a variety of carboxylic acid derivatives. These observations will have important implications for the design and optimization of new processes involving Sm(II)-reduction of ketyl radicals. (Chemical Equation Presented).

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Synthesis/biological evaluation of hydroxamic acids and their prodrugs as inhibitors for Botulinum neurotoxin A light chain

Botulinum neurotoxin A (BoNT/A) is the most potent toxin known Unfortunately, it is also a potential bioweapon in terrorism, which is without an approved therapeutic treatment once cellular intoxication takes place Previously, we reported how hydroxamic acid prodrug carbamates increased cellular uptake, which translated to successful inhibition of this neurotoxin Building upon this research, we detail BoNT/A protease molecular modeling studies accompanied by the construction of small library of hydroxamic acids based on 2,4-dichlorocinnamic hydroxamic acid scaffold and their carbamate prodrug derivatization along with the evaluation of these molecules in both enzymatic and cellular models

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

Archives for Chemistry Experiments of 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

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Manganese(I)-Catalyzed beta-Methylation of Alcohols Using Methanol as C1 Source

Highly selective beta-methylation of alcohols was achieved using an earth-abundant first row transition metal in the air stable molecular manganese complex [Mn(CO)2Br[HN(C2H4PiPr2)2]] 1 ([HN(C2H4PiPr2)2]=MACHO-iPr). The reaction requires only low loadings of 1 (0.5 mol %), methanolate as base and MeOH as methylation reagent as well as solvent. Various alcohols were beta-methylated with very good selectivity (>99 %) and excellent yield (up to 94 %). Biomass derived aliphatic alcohols and diols were also selectively methylated on the beta-position, opening a pathway to ?biohybrid? molecules constructed entirely from non-fossil carbon. Mechanistic studies indicate that the reaction proceeds through a borrowing hydrogen pathway involving metal?ligand cooperation at the Mn-pincer complex. This transformation provides a convenient, economical, and environmentally benign pathway for the selective C?C bond formation with potential applications for the preparation of advanced biofuels, fine chemicals, and biologically active molecules.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Cu-catalyzed aerobic oxidative esterification of acetophenones with alcohols to I¡À-ketoesters

Copper-catalyzed aerobic oxidative esterification of acetophenones with alcohols using molecular oxygen has been developed to form a broad range of I¡À-ketoesters in good yields. In addition to reporting scope and limitations of our new method, mechanism studies are reported that reveal that the carbonyl oxygen in the ester mainly originated from dioxygen.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Iron-catalyzed reduction of carboxylic esters to alcohols

A novel catalytic system formed from Fe(stearate)2/NH 2CH2CH2NH2 and polymethylhydrosiloxane was directly developed for the hydrosilylation of carboxylic acid esters to alcohols. The catalytic method exhibits broad substrate scope, including 20 aliphatic, aromatic, and heterocyclic esters. The corresponding alcohols are obtained in moderate to very good yields. The first iron-catalyzed hydrosilylation of carboxylic acid esters to alcohols is described. A catalytic system formed by Fe(stearate)2/NH 2CH2CH2NH2 and polymethylhydrosiloxane (PMHS) is used for this transformation, which has a broad substrate scope, including 20 aliphatic, aromatic, and heterocyclic esters. The corresponding alcohols are obtained in moderate to very good yields. Copyright

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

Discovery of 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 214894-89-0, and how the biochemistry of the body works.Formula: C9H9BrO2

In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 214894-89-0, name is 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine, introducing its new discovery. Formula: C9H9BrO2

BETA-AMYLOID PROTEIN PRODUCTION/SECRETION INHIBITORS

Provided are novel compounds having an inhibitory activity against production or secretion of beta-amyloid protein. They embrace compounds represented by the following formula (1): and capable of being replaced with a variety of substituents; and salts thereof, and solvates of any one of them.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Regioselective hydroboration-oxidation and -amination of fluoro-substituted styrenes

Hydroboration of fluorinated styrenes with common hydroborating agents results in polymerization. However, regioselective hydroboration has been achieved by utilizing iodoborane-dimethyl sulfide. A series of fluorinated beta-phenethyl alcohols and amines were synthesized via this methodology.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem