Archives for Chemistry Experiments of 1-(Benzo[d]oxazol-2-yl)ethanone

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A formal synthesis of (+)-didemniserinolipid B employing a Pd-mediated 6-endo selective alkynediol cycloisomerization

Herein, we describe a concise assembly of central 6,8-dioxabicyclo[3,2,1]octane core of didemniserinolipid by employing a Pd-mediated alkynediol cycloisomerization and a formal total synthesis of didemniserinolipid B.

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Photoredox-induced three-component Oxy-, Amino-, and Carbotrifluoromethylation of enecarbamates

A photoredox-catalzyed trifluoromethylation of enecarbamates process is reported. This pathway uses Togni’s reagent as the CF3 source and follows a radical/cationic pathway. Under the optimized conditions using [Ru(bpy)3(PF6)2] as the photocatalyst, a wide range of substituted enecarbamates can readily be difunctionalized by means of various O, N, and C nucleophiles.

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Assembling heterocycle-tethered C-glycosyl and alpha-amino acid residues via 1,3-dipolar cycloaddition reactions

(Equation Presented) The 1,3-dipolar cycloadditions of C-glycosyl nitrile oxides and acetylenes to an alkyne and an azide, respectively, bearing a masked glycinyl moiety furnished disubstituted isoxazoles and triazoles. Unveiling the glycinyl group in these cycloadducts afforded C-glycosyl alpha-amino acids in which the two bioactive entities were tethered through rigid five-membered heterocycles. Optimized entries to the same compounds involved the use of unmasked but protected alkyne- and azide-containing amino acids as the partners of 1,3-dipolar cycloadditions.

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Synthesis of (+)-didemniserinolipid B via ketalization/ring-closing metathesis

A modular synthesis of didemniserinolipid B is reported. Central to this synthesis was the use of a ketalization/ring-closing metathesis (K/RCM) strategy to establish the 6,8-dioxabicyclo[3.2.1]octane core. The C10 axial alcohol was established via a selective epoxidation, followed by reductive trans-diaxial epoxide opening. The serinol and unsaturated ester side chains were introduced by a Williamson etherification and cross metathesis, respectively.

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Synthesis of novel 2,3,4-trisubstituted-oxazolidine derivatives and in Vitro cytotoxic evaluation

We have previously reported the discovery of cytotoxic and pro-Apoptotic hit compound 1,1-dimethylethyl (S)- 2,2-dimethyl-4-[(3-nitrophenoxy)methyl]-3- oxazolidinecarboxylate 1 against leukemia cells. In the present work we describe the synthesis of 25 derivatives of this hit varying the substituent at ring or stereochemistry of the oxazolidine ring and evaluated them against human cancer cells lines. Six compounds exerted significant activity against HL60 promyelocytic leukemia cells with IC50 in low micromolar range (4-18 muM) and three compounds displayed activity against MDA-MB231 breast cancer cells (25-37 muM). In vitro cytotoxicity on normal cells PBMC (human peripheral blood mononuclear cells) was also evaluated. Compounds 7e (p-NO2, S) and 7m (p-COOCH3, S) showed good antiproliferative activity against HL60 (4 and 5 muM) and MDA-MB231 (37 and 25 muM) without affecting lymphocyte proliferation in PBMC, indicating low toxicity to normal cells. Besides, compound 7e induced DNA fragmentation on about 100% of HL60 cells at 50 muM. In this case, it was more potent than 7m and lead 1. This indicated that compound 7e has a great pro-Apoptotic potential.

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Formal synthesis of (+)-didemniserinolipid B

The formal synthesis of (+)-didemniserinolipid B is achieved using Weinreb reaction, Yadav’s chiral propargyl alcohol protocol and hydrolytic ketal formation as the key steps.

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3-(2-Acylamino-1-Hydroxyethyl)-Morpholine Derivatives and Their Use as Bace Inhibitors

The present invention provides BACE inhibitors of Formula (I); methods for their use and preparation, and intermediates useful for their preparation.

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The Synthesis and Configurational Stability of Differentially Protected beta-Hydroxy-beta-amino Aldehydes

Syntheses of 1,1-dimethylethyl (S)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate (5) and 1,1-dimethylethyl (4S-trans)-4-formyl-2,2,5-trimethyl-3-oxazolidinecarboxylate (6) from commercially available serine and threonine derivatives are described.The method involves selective reduction of the corresponding oxazolidine esters 3 and 4 using diisobutylaluminum hydride at low temperature.These differentially protected beta-hydroxy-alpha-amino aldehydes are also shown to be produced in 93-95 percent enantiomeric excess (via NMR and HPLC analysis of the Mosher esterderivatives 8 and epi-8)-thus making them useful as chiral, nonracemic synthons for asymmetric synthesis.

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A stereodivergent route to four stereoisomeric 3?- acetoxycyclopentenylglycine derivatives

A short and efficient synthetic route to four stereoisomeric 3-acetoxycyclopentenylglycine derivatives from l-serine has been developed. The method features a stereoselective conjugate addition and ring-closing metathesis as key steps. Georg Thieme Verlag Stuttgart ¡¤ New York.

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OXAZOLIDIN-2-ONE COMPOUNDS AND USES THEREOF

The present invention relates to oxazolidin-2-one substituted pyrimidine compounds that act as PI3K (phosphatidylinositol-3-kinase) inhibitors, as well as pharmaceutical compositions thereof, methods for their manufacture and uses for the treatment of conditions, diseases and disorders dependent on PI3K

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