Extracurricular laboratory:new discovery of 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)ethanone

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A novel method for preparing Eligulstat through chiral resolution

Eliglustat is a ceramide glucosyltransferase inhibitor work as first line oral therapy for adults with Gaucher disease type 1 (a rare disease) at present. Although the eliglustat in enantiomerically pure forms is obtained by asymmetric syntheses, the reported methods suffer from many limits when it comes to industrial applications. Therefore, the preparation of a racemic mixture followed by resolution can still be a viable and straightforward alternative, especially when it could be adapted to large scale. Herein, we developed an effective and practical synthetic route to prepare stereoisomers mixture of eliglustat, and a novel chiral resolution method to prepare eliglustat. Using 1,1?-Binaphthyl-2,2?-diyl -hydrogenphosphate (BNDHP) as resolution reagent, optical pure eliglustat (e.e. >99%, 13.97% total yield) could be obtained after recrystallization.

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

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Synthesis, biological evaluation and quantitative structure-active relationships of 1,3-thiazolidin-4-one derivatives. A promising chemical scaffold endowed with high antifungal potency and low cytotoxicity

With reference to recent studies reporting on the various biological properties of the thiazolidinone scaffold, we synthesized more than a hundred compounds characterized by a 1,3-thiazolidin-4-one nucleus derivatised at the C2 with a hydrazine bridge linked to (cyclo)aliphatic or hetero(aryl) moieties, and their N-benzylated derivatives. These molecules were assayed as potential anti-Candida agents and they were shown to possess comparable, and in some cases higher biological activity than well-established topical and systemic antimycotic drugs (i.e. clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Compounds endowed with the lowest MICs underwent further testing in order to assess their cytotoxic effect (CC50) on Hep2 cells, which demonstrated their relative safety. Finally, QSAR and 3-D QSAR models were used to predict putative chemical modifications of the 1,3-thiazolidin-4-one scaffold in order to design new and potential more active compounds against Candida spp.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Reactions of Carbonyl Compounds with Benzyl Chloromethyl Ether of Diiodomethane in the Presence of Samarium(II) Iodide or Metallic Samarium. New Routes to 1,2-Diols, Iodohydrins and Cyclopropanols

Carbonyl compounds react with benzyl chloromethyl ether in the presence of samarium(II) iodide to afford the corresponding addition products which, when subsequently hydrogenolysed, yield 1,2-diols.Simple aldehydes and ketones react with diiodomethane in the presence of samarium metal to give iodohydrins in good yields.Under similar reaction conditions, alpha-halogeno substituted ketones and aromatic 1,4-diketones are converted into cyclopropanols.These cyclopropanations have been shown to rpoceed through the initial generation of samarium enolates, followed by the Simmons-Smith type reaction.A novel transformation of esters to cyclopropanols via tandem one-carbon homologation is also described.

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

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Unusual behaviour of 7-diethylamino-3-(3,4-ethylen-dioxybenzoyl)coumarin towards Group IIA cations: A potential photoactive probe for magnesium

The titled compound showed, upon spectrophotometric titrations with Group II cations, a spectacular bathochromic shift (c.a. 50 nm) with Mg2+ but not with the other cations. This result is – understood in terms of internal charge-transfer species expressly favored by Et2N and ArCO substituents and best matching of ionic diameter and charge density of Mg2+. This finding may lead to new simple photoactive probes.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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A new protocol for the construction of pyrrolo[4,3,2-de]quinolinones

A facile method has been suggested for constructing pyrrolo[4,3,2-de]quinolinones by addition of acetophenones to 4-nitroisatin followed by reduction of the nitro group and spontaneous cyclisation.

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

Discovery of 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)ethanone

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Hydrochloric acid as an efficient catalyst for intermolecular condensation of alcohols. A simple and highly efficient synthesis of unsymmetrical ethers from benzylic alcohols and alkanols

Benzylic alcohols and diarylmethanols with electron-donating substituents in the aromatic ring reacted with aliphatic alcohols in the presence of a catalytic amount of HCl to give the corresponding alkyl arylmethyl ethers. The reactivity of diarylmethanols in the intermolecular dehydration depended on the nature of substituents in the aromatic rings and structure of aliphatic alcohol.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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PURINE DERIVATIVES USEFUL AS HSP90 INHIBITORS

The present application provides substituted purine derivatives and related compounds of the formulas shown. These compounds are useful as inhibitors of HSP90, and hence in the treatment of related diseases. (Formulae) Z1-Z3 , Xa-Xc, X2 , 324, Y and R are as defined in the specification

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Utilizing Mor-DalPhos/palladium-catalyzed monoarylation in the multicomponent one-pot synthesis of indoles

The application of a Mor-DalPhos/palladium catalyst system in the one-pot, multicomponent assembly of substituted indoles from ortho-chlorohaloarenes, alkyl ketones (including acetone), and primary amines is reported. The described protocols offer improved substrate scope in all three reaction components, under more mild conditions and without the need for an additional drying agent. Also reported are the first examples of such multicomponent reactions where all reactants are combined at the start of the reaction, without the need for inert atmosphere reaction conditions.

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

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Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 mumol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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6-CYCLOPROPYL- AND 6-(1-METHYLCYCLOPROPYL)-1,4-BENZODIOXANES: SYNTHESIS AND NITRATION. REARRANGEMENT OF NITRO SUBSTITUTED 6-CYCLOPROPYL-1,4-BENZODIOXANES USING CONCENTRATED SULFURIC ACID

6-Cyclopropyl- and 6-(1-methylcyclopropyl)-1,4-benzodioxanes have been synthesized as the first cyclopropyl-1,4-benzodioxanes.It was shown that nitration of these compounds occurs with retention of the three carbon ring.In contrast to simple ethers of cyclopropylphenols, nitration leads only to 7-nitro-6-cyclopropyl- and 7-nitro-6-(1-methylcyclopropyl)-1,4-benzodioxanes, respectively.Nitration of 7-nitro-6-cyclopropyl-1,4-benzodioxane occurs regioselectively to give exclusively the 7,8-dinitro product.The structure of the nitration products was confirmed by their rearrangement to the corresponding nitrosopropionyl-1,4-benzodioxanes.

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