Fluoroalkyl substituted (Z)-dehydro α-amino ester as a building block for the fluorine-containing cyclopropyl α-amino esters and dihydrooxazole

Multi-functionalized β-trifluoromethyl and β-difluoromethyl substituted (Z)-α,β-dehydro α-amino esters have been successfully prepared from N-protected fluorinated threonine ester. Applications of this new fluorine-containing building block to the synthesis of biologically important fluorinated cylcopropyl α-amino esters and dihydrooxazole ester have also been reported.     

From fluoral to heterocycles: a survey of polyfluorinated iminiums chemistry

Hemiaminals of fluorinated aldehydes are very useful reagents. They are able, under Lewis acid activation, to generate iminium species which can react with various nucleophiles and provide diverse fluorinated compounds. By this methodology, β-fluoroalkylated enones, which are very interesting building blocks, have been easily obtained. Fluorinated homoallylamines have been also synthesized and used as starting material to prepare α-fluoroalkylated nitrogen heterocycles. Many other synthetic applications of these fluorinated iminium ions provide new bioactive compounds.     

Henry reaction of fluorinated nitro compounds

The Henry (nitroaldol) reaction of fluorinated nitro compounds with various aromatic aldehydes and a fluorinated aliphatic aldehyde to give β-fluoro-β-nitroalcohols which bearing a fluorinated quaternary carbon center was reported. The relative configuration of the major diastereoisomer of 2-fluoro-2-nitro-1-(4-nitrophenyl)-3-phenylpropanol (5bf) was determined by X-ray single crystal analysis.     

基于β-环糊精接枝聚L-谷氨酸星型聚合物的可注射水凝胶的制备与表征

采用Gadelle-Defaye法制备了全-6-氨基-β-环糊精[β-CD-(NH2)7],并用"Grafting-from"接枝法得到不同分子量的星型结构β-环糊精-g-聚L-谷氨酸(β-CD-g-PLGA).对β-CD-g-PLGA进行酰肼化改性后与醛基化海藻酸钠(ALG-CHO)通过席夫碱交联反应制备β-CD-g-PLGA/ALG水凝胶.研究了前驱体浓度以及β-CD-gPLGA分子量对β-CD-g-PLGA/ALG水凝胶性能的影响,并以疏水性辛伐他汀(SIM)为模型药物,研究了水凝胶对SIM的控制释放行为.     

Trialkyl borate assisted amination of fluorinated 1,3-diketones for synthesis of N,N′-1,2-phenylen-bis(β-aminoenones) and their Ni(II), Cu(II) and Pd(II) complexes

An effecient synthetic method for fluorinated tridentate β-aminoenones and tetradentate bis(β-aminoenones) via amination of fluorinated 1,3-diketones with o-phenylenediamine in the presence of trialkyl borates was developed. Ni(II), Cu(II) and Pd(II) complexes with tetradentate bis(β-aminoenones) were obtained. Their gaschromatographic behaviour and main fragmentation paths in the electron ionization mass spectra were described.     

Synthesis of β-fluoro-β-proline

A synthetic strategy towards the novel amino acid β-fluoro-β-proline, a fluorinated analogue of β-proline, is elaborated. The synthesis commences from commercially available methyl 2-fluoroacrylate and involves three steps. The overall yield of β-fluoro-β-proline is 57%.     

Fluorinated β-lactones and poly(β-hydroxyalkanoate)s: synthesis via epoxide carbonylation and ring-opening polymerization

Efficient and mild reaction conditions were developed for the catalytic carbonylation of fluorinated epoxides to their corresponding β-lactones. Six new lactones with fluorinated side chains were prepared in high isolated yields. These lactones were polymerized to form a series of new poly(β-hydroxyalkanoate)s with fluorinated side chains, and their properties were examined with respect to their hydrocarbon analogs. Finally, copolymerizations were performed with fluorinated lactones and β-butyrolactone, which resulted in tapered copolymers rather than the expected random copolymers.     

An efficient Fe(III)-catalyzed 1,6-conjugate addition of para-quinone methides with fluorinated silyl enol ethers toward β,β-diaryl α-fluorinated ketones

Reported here is a highly efficient 1,6-conjugate addition of fluorinated silyl enol ethers to para-quinone methides, allowing facile access to a range of β,β-diaryl α-fluorinated ketones with good to high yields. Fe(OTf)₃ was identified as the optimal catalyst, with the loading of 3?mol%. Notably, this represent the first 1,6-conjugate addition with fluorinated silyl enol ethers. The synthetic potential of the resulting adducts is also demonstrated.     

Gold-catalyzed synthesis of β-trifluoromethylated α,β-unsaturated ketones from CF3-substituted propargylic carboxylates and their reactivity in Diels-Alder reactions

The synthesis of fluorinated synthetic intermediates has become a field of intense research in organic chemistry. In this article, we report the application of a gold-catalyzed rearrangement to the synthesis of β-trifluoromethylated α,β-unsaturated ketones. The scope of the reaction, as well as the valorization of the products in subsequent transformations has been investigated. This study allowed for the preparation of various CF₃-substituted enones and fluorinated Diels-Alder adducts from easily accessible starting materials.     

Syntheses of fluorine-containing mucin core 2/core 6 structures using novel fluorinated glucosaminyl donors

Syntheses of fluorinated mucin core 6 disaccharides and core 2 trisaccharides modified at the C-3 or C-4 position of the pertinent glucosamine residue required for mechanistic study of glycosyltransferases and sulfotransferases involved in the biosynthesis of O-glycans are reported. Novel fluorinated glucosaminyl donors were synthesized from 2-naphthylmethyl β-d-N-acetylglucosamine (β-O-NAP-GlcNAc) via double inversion of the C-3 or C-4 configuration. A one-step β-alkylation of GlcNAc was reported for the first time to afford β-O-NAP-GlcNAc in high yield, which constitutes the cornerstone of the synthetic strategy based on NAP-glycosides in oligosaccharides synthesis.     

Facile synthetic pathway to β-hydroxy-β-trifluoromethyl imines and their derivatives

Synthetic approach based on mediated addition of different trifluoromethylated building blocks to selected acyclic imines giving access to a variety of β-hydroxy-β-trifluoromethyl imines are elaborated. A reaction between fluorinated adducts and imines proceed easily giving the condensation products in good to excellent yields. β-Hydroxy-β-trifluoromethyl imines possessing trifluoromethyl group and exhibiting strong intramolecular hydrogen bonding are great precursors to different β-hydroxy-β-trifluoromethyl ketones and alcohols.     

Extractions with β-diketones as chelating solvents

This study was undertaken to prepare a liquid compound with low water solubility which would form metal chelates readily and also act in the dual role of organic solvent in the solvent extractions of metal chelates. The compounds 7-methyl-2,4-octanedione and 1,1,1-trifluoro-7-methyl-2,4-octanedione were prepared and their P and K values determined. Radiotracer distribution studies with 9 metals indicate that the stated goal was reached. The observed distribution coefficients for the majority of the metals were much larger than those obtained with another pure β-diketone, acetylacetone. Also, extractions occur at lower pH values. Ion-pair phenomena are indicated in several cases. The principal general difference between the fluorinated and non-fluorinated β-diketones is a shift in the distribution curves towards the acid region for the fluorinated compounds.     

A new synthetic approach to 2,3-dideoxy-2-fluoro-β-d-threo-pentofuranose, the fluorofuranose unit of the anti-HIV-active nucleoside, β-FddA

The fluorinated furanose unit of the anti-HIV-active nucleoside (2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine, β-FddA, has been synthesized as its 5-trityl derivative with high stereocontrol from (S)-trityl glycidol and phenylthioacetic acid.     

Preparation of Polymeric Membranes Entrapping β-Cyclodextrins and Their Molecular Recognition of Naringin

An amorphous polyetheretherketone known as PEEK-WC and a β-cyclodextrin derivative (O-octyloxycarbonyl-β-CD), insoluble in water, were used to prepare flat sheet membranes by the diffusion induced phase separation. It was found that the β-CD derivative entrapped in membranes is able to form a complex with naringin, a bitter component present in grapefruits. The recognition properties of the β-CD derivative immobilized in the PEEK-WC membranes towards naringin have been investigated as a function of the amount of β-CD derivative present in the casting solution. A significant improvement of the efficiency of theO-octyloxycarbonyl-β-CD was observed when an inclusion complex with naringin in the membrane was formed compared to when the β-CD derivative is dispersed in an aqueous solution of naringin. Washing with an alkaline solution allows an easy regeneration of the membranes and permits their reuse. No recognition properties were found for PEEK-WC membranes made without the β-CD derivative.     

Stereoselective epoxidation of 4-fluoro-4-nitrocyclohexenes

Novel fluorinated α-epoxycyclohexanes were synthesized in up to 96% yields by epoxidation of the Diels–Alder adducts of β-fluoro-β-nitrostyrenes and 2,3-dimethylbuta-1,3-diene. The epoxidation with m-chloroperoxybenzoic acid and subsequent hydrolysis into diols were found to proceed in a highly stereoselective manner.     

High‐expression β1 adrenergic receptor/cell membrane chromatography method based on a target receptor to screen active ingredients from traditional Chinese medicines

β‐Adrenergic receptors are important targets for drug discovery. We have developed a new β₁‐adrenergic receptor cell membrane chromatography (β₁AR‐CMC) with offline ultra‐performance LC (UPLC) and MS method for screening active ingredients from traditional Chinese medicines. In this study, Chinese hamster ovary‐S cells with high β₁AR expression levels were established and used to prepare a cell membrane stationary phase in a β₁AR‐CMC model. The retention fractions were separated and identified by the UPLC–MS system. The screening results found that isoimperatorin from Rhizoma et Radix Notopterygii was the targeted component that could act on β₁AR in similar manner of metoprolol as a control drug. In addition, the biological effects of active component were also investigated in order to search for a new type of β₁AR antagonist. It will be a useful method for drug discovery as a leading compound resource.     

Synthesis of block and graft copolymers of β-pinene and styrene by transformation of living cationic polymerization to atom transfer radical polymerization

The transformations of living cationic polymerization to ATRP to form the block and graft copolymers of β-pinene with styrene were performed. Poly(β-pinene) carrying benzyl chloride terminal [poly(β-p)StCl] was prepared by capping the living poly(β-pinene), which was obtained with 1-phenylethyl chloride/TiCl₄/Ti(OiPr)₄/nBu₄NCl initiating system, with a few units of styrene. Poly(β-p)StCl, in conjunction with CuCl and bpy, could initiate the ATRP of styrene and gave well-defined block copolymer of β-pinene and styrene. In contrast, tert-alkyl-chlorine-capped poly(β-pinene) [poly(β-p)Cl] obtained by living cationic polymerization of β-pinene per se without capping of styrene gave a mixture of desired block copolymers and unreacted poly(β-p)Cl due to the low initiating reactivity of poly(β-p)Cl. Brominated poly(β-pinene) synthesized by the quantitative bromination of poly(β-pinene) using NBS was also used to initiate the ATRP of styrene in the presence of CuBr and bpy to prepare the graft copolymer of β-pinene and styrene. The first-order kinetic characteristic and linear increment of molecule weight with the increasing of monomer conversion indicated the living nature of this ATRP grafting.     

Inclusion complexes of fluconazole with β-cyclodextrin: physicochemical characterization and in vitro evaluation of its formulation

Fluconazole (FZ) is a triazole antifungal drug administered orally or intravenously. It is employed for the treatment of mycotic infections. However, the efficacy of FZ is limited with its poor aqueous solubility and low dissolution rate. One of the important pharmaceutical advantages of cyclodextrins is to improve pharmacological efficacy of drugs due to increasing their aqueous solubility. The aim of present study was to prepare an inclusion complex of FZ and β-cyclodextrin (β-CD) to improve the physicochemical and biopharmaceutical properties of FZ. The effects of β-CD on the solubility of FZ were investigated according to the phase solubility technique. Complexes were prepared with 1:1 M ratio by different methods namely, freeze-drying, spray-drying, co-evaporation and kneading. For the characterization of FZ/β-CD complex, FZ amount, practical yield %, thermal, aqueous solubility, XRD, FT-IR and NMR (¹H and ¹³C) analysis were performed. In vitro dissolution from hard cellulose capsules containing FZ/β-CD complexes was compared to pure FZ and its commercial capsules and evaluated by f₁ (difference) and f₂ (similarity) factors. Paddle method defined in USP 31 together with high pressure liquid chromatographic method were used in in vitro dissolution experiments. It was found that solubility enhancement by FZ/β-CD complexes depends on the type of the preparation method. High release of active agent from hard cellulose capsules prepared with β-CD complexes compared to commercial capsules was attributed to the interactions between β-CD and active agent, high energetic amorphous state and inclusion complex formation.     

Synthesis of a new fluorinated oxazolidinone and its reactivity as a chiral auxiliary in Aldol reactions

A new enantiomerically pure fluorinated oxazolidinone has been prepared from a fluorinated imidoyl chloride and an optically pure sulfoxide. The diastereoselective reduction of the β-iminosulfoxide thus formed followed by elimination of the sulfoxide and cyclization of the created aminoalcohol furnishes the desired product. The fluorinated oxazolidinone was subsequently used as a chiral auxiliary in Aldol reactions. We also found that the selective formation of the syn-Evans and syn-non-Evans diastereoisomer can be controlled by adjusting the Lewis acid/base ratio.     

Facile allylboration of ketones with β-benzyloxy-γ,γ-difluoroallylboronate: Preparation of gem-difluorinated homoallylic tert-alcohols

The reaction of β-benzyloxy-γ,γ-difluoroallylboronate, at room temperature and in the absence of catalysts, with a variety of aromatic and aliphatic ketones of varying sterics and electronic requirements furnishes fluorinated homoallylic tert-alcohols in 62-82% yields. Representatives of these alcohols were converted to their corresponding α,α-difluoro-β-hydroxy ketones in 73-85% yields.