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A nanocatalyst with chiral amino alcohol catalytic function was efficiently employed in the Henry reaction, easily recovered by centrifugation and reused without loss of activity.

Herein, the synthesis and catalytic activity of two ephedrine-based catalysts and two ephedrine-based magnetic nanoparticle-supported catalysts are reported. All catalysts developed were tested in the addition of diethylzinc to aromatic aldehydes and in the Henry reaction. The homogeneous catalysts showed moderate catalytic activity in the organozinc addition and good activity in the Henry reaction, whereas in the case of the nanocatalyst, it was not effective in the addition of diethylzinc to aldehydes and gave reasonable results in the Henry reaction. Moreover, the nanocatalyst remained unchanged over the course of up to three catalytic cycles. To the best of our knowledge, the proposed system is the first recyclable ephedrine-based magnetic nanocatalyst employed in an enantioselective reaction.

Fluorescent atomically precise Ag38(11-azido-2-ol-undecane-thiolate)24 nanoclusters are easily prepared using sodium ascorbate as a "green"reducer and are extensively characterized by way of elemental analyses, ATR-FTIR, XRD, SAXS, UV-vis, fluorescence spectroscopies, and theoretical modeling. The fluorescence and the atomically determined stoichiometry and structure, the facile and environmentally green synthesis, together with the novel presence of terminal azido groups in the ligands which opens the way to "click"-binding a wide set of molecular species, make Ag38(11-azido-2-ol-undecane-thiolate)24 nanoclusters uniquely appealing systems for biosensing, recognition and functionalization in biomedicine applications and in catalysis. This journal is

With the aim to easily recover and reuse the catalyst, an efficient amino alcohol catalyst previously tested in the asymmetric addition of diethylzinc to several aromatic aldehydes has been immobilized on proper functionalized superparamagnetic core-shell magnetite-silica nanoparticles and employed in the Henry reaction in the semi-homogeneous phase. The nanocatalyst exhibits a promising catalytic activity that remains unchanged in the three catalytic cycles performed. The results prove that highly efficient catalysts, by being immobilized on suitable magnetic nanosupports, can be easily recovered and reused, maintaining their catalytic behavior.

Fluorescent atomically precise Ag

The first stereocontrolled total synthesis of iminosugar 1,4-dideoxy-1,4-imino-D-iditol is described. The key step in our approach was the double diastereoselection in the asymmetric dihydroxylation (AD) of suitable optically active olefin, the chiral vinyl azido alcohol 9. Performing the AD using the most common Cinchona alkaloids as ligands enabled us to identify the ligand of choice for the stereodivergent synthesis of 1,4-dideoxy-1,4-imino-D-iditol and 1,4-dideoxy-1,4-imino-D-galactitol. These type of iminosugars, both natural and unnatural, are intensively studied for their promising chemotherapeutic properties against viral infections, diabetes, cancer, and tuberculosis.

Herein we describe a versatile approach to the pyrrolizidine alkaloids skeleton by tailoring our original strategy already used for the pyrrolidine iminosugars synthesis. The key steps are the regio- and stereoselective azidolysis of the suitable chiral vinyl epoxide and then asymmetric dihydroxylation of the corresponding azido alcohol by using (DHQ)2AQN as the ligand. Further optimized elaborations addressed to the closure of the two rings allowed us to achieve the target iminosugar with complete stereocontrol. The wide range of pyrrolizidine iminosugars’ biological properties make them a key focus of new drug research and therefore the development of synthetic strategies for obtaining them is of decisive importance.

A study aimed at the synthesis and structure optimization of new, efficient, optically active β-amino alcohol ligands with a structure suitable for immobilization on magnetite nanoparticles has been carried out. The optimized homogeneous amino alcohol catalysts 13a and 13b, the chirality of which arises from the Sharpless epoxidation of suitable allyl alcohols, were tested by employing the well-established enantioselective amino alcohol-promoted addition of diethylzinc to benzaldehyde, giving the corresponding benzyl alcohol with nearly quantitative yield and ee = 95%. Then, their broad applicability as chiral catalysts was evaluated by carrying out the same reaction on a family of aldehydes, including variously substituted aromatic ones as well as an aliphatic analogue. The results have confirmed the validity of the fine-tuning process performed on ligands 13a and 13b. In fact, both exhibited excellent catalytic activity as demonstrated by the chemical yields and ee obtained from all the tested aldehydes, almost independent of the position and type of substitution in the aromatic ring.

Negletein has been shown to have therapeutic potential for inflammation-associated diseases, but its effect on neurite outgrowth is still unknown. The present study showed that negletein alone did not trigger PC12 cells to differentiate and extend neurites. When compared with the cells in the untreated control, a significant (P

A study of the stereochemical control on the asymmetric dihydroxylation of the double bond of optically active vinyl epoxides and their derivatives (bromo derivatives, azido derivatives, and vinyl aziridines) was carried out and the obtained results are herein reported. The most interesting results were obtained on trans α,β-unsaturated epoxy esters, which were successfully converted with a diastereomeric ratio >80% into the corresponding diols using either the matched or the mismatched conditions, depending on the ligand used. Unprotected bromo derivatives and unprotected aziridines did not afford significant results, while for the protected bromo derivatives, azido derivatives, and N-Boc protected aziridines the matched conditions led to a diastereomeric ratio >95%. Chirality 28:387-393, 2016. © 2016 Wiley Periodicals, Inc.

Drawing inspiration from the structural features of some natural polyphenols, the synthesis of two different model compounds as potential inhibitors of HIV integrase (IN) has been described. The former was characterised by a diketo acid (DKA) bioisostere, such as a β-hydroxycarbonyl moiety, between two fragments containing aromatic groups, while in the latter an epoxide linked two polyoxygenated aromatic residues. The moieties present in the structures are thought to function by chelating divalent metal ions on the enzyme catalytic site. Overall, 10 compounds were prepared and some of that submitted to molecular modelling studies (to investigate their interactions with the active site of IN), to metal titration studies (to detect their chelating capability) and to biological assays.

The increased accumulation of iron in the brain in Alzheimer's disease (AD) is well documented, and excess iron is strongly implicated in the pathogenesis of the disease. The adverse effects of accumulated iron in AD brain may include the oxidative stress, altered amyloid beta-metabolism and the augmented toxicity of metal-bound amyloid beta 42. In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased β-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in β-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone negletein (5,6-dihydroxy-7-methoxyflavone), which is a known chelator for iron, can significantly prevent the effects of FAC on APP metabolism in SHSY5Y cells. Further, this compound inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. In concentrations used in this study, negletein alone appears to have only marginal toxic effects on cell viability, but, on the other hand, the drug is capable of ameliorating the iron-induced loss of cell viability considerably. Our results provide the initial evidence of potential therapeutic effects of negletein, which should be explored in suitable animal models of AD.

The Lewis acid-catalyzed regioselective azidolysis of 2,3-three membered heterocyclic amines has been investigated. The results obtained demonstrated that using TMSN3 as a source of azide, the appropriate choice of Lewis acid allowed to obtain different regio- and stereocontrolled precursors of aminoalcoholic and triaminic sequences. Considering the occurrence of these moieties in the structure of many biologically active compounds, the present methodologies could represent a powerful tool in organic synthesis for the preparation of interesting molecules.

Herein the total synthesis of the pyrrolidine alkaloids 1,4-dideoxy-1,4-imino-d-galactitol and its diastereoisomer 1,4-dideoxy-1,4-imino-d-glucitol is described, starting from a common optically active precursor. The key step in our approach was the double diastereoselection in the asymmetric dihydroxylation of chiral vinyl azido alcohols, obtained by means of two different regio- and stereoselective nucleophilic openings of the corresponding chiral vinyl epoxide.

A stereocontrolled, facile and high-yield approach for producing (+)-altroDNJ, has been developed starting from the inexpensive commercial cis 2-butene-1,4-diol. Sharpless epoxidation and a subsequent dihydroxylation were used for the introduction of all stereocentres; finally, the ring closure under basic conditions afforded the piperidine heterocycle.

A convenient strategy for the preparation of compounds bearing the benzofuran skeleton starting from tyrosol, a phenol largely present in olive oil production waste, with no biological importance, is reported. A bromination/methoxylation sequence, already described for the synthetic transformation of naturally occurring compounds, was exploited. Depending on the solvent used for the methoxylation reaction together with the presence of a 4-phenol moiety respect to the side chain, benzodihydrofurans or a benzofurans derivative can be obtained.

An easy and general azidolysis of vinylepoxides mediated by BF3·OEt2 and TMSN3 recently reported by our group has been extended to vinylaziridines. The reaction affords unsaturated azido derivatives with complete stereoselectivity and regioselectivity, when in the presence of electron-poor olefins, regardless of the size of substituents on the heterocyclic ring.

Starting from 2,3-aziridine alcohols, a novel and versatile preparation of optically active amino polyol was achieved using a simple strategy with few purification steps and a good overall yield.

An expeditious synthesis of three polyoxygenated flavones mosloflavone, negletein and baicalein. starting from crysin, an easily available flavone, by a bromination/methoxylation procedure is reported The convergent synthesis exploits a base induced Wesley-Moser type rearrangement (C) 2009 Elsevier Ltd All rights reserved

A novel and efficient one-pot stereoselective transformation of N-(t-butoxycarbonyl)-2,3-aziridino alcohols into 4-substituted and 4,5-disubstituted oxazolidin-2-ones has been developed; these functionalized products are amenable to other elaborations, some of which are described. (C) 2007 Elsevier Ltd. All rights reserved.

Starting from a single suitable functionalised epoxide, a highly efficient stereoselective synthesis of d - erythro -sphingosine and d - lyxo -phytosphingosine is described. The approach allows the formal preparation of all stereoisomers of these sphingoid structures.

The stereocontrolled condensation of methyl ketones to trans alpha,beta-aziridine aldehydes creates functionalized aldols, valuable precursors for different amino hydroxylated structures, such as amino alcohols, amino diols, alpha-tetrahydrofuryl amides, and alpha-furyl amides.

An efficient and simple one-pot procedure for selective etherification of 2-aryl-ethylalcohols has been achieved through Amberlyst 15-catalyzed reaction in dimethyl carbonate (DMC). Moreover, the polymer catalyst could be recovered and reused with no effect on its activity. The reaction mechanism involves the formation of phenonium ion which has been demonstrated by a C-C bond forming reaction. Theoretical studies are in agreement with and thus explain experimental results. (C) 2013 Elsevier Ltd. All rights reserved.

The results obtained in the MgBr2‐mediated opening of 2,3‐bifunctionalised aziridines are reported. The study shows that, at least for the Z stereoisomers, the bromide attacks the aziridine ring in the α position to all functional groups considered with high regioselectivity, thus suggesting a strong aptitude for MgBr2 to coordinate a benzyloxy function.

Peptidic aminopeptidase inhibitors, bestatin, phebestin and probestin have been prepared by stereo- and regiocontrolled reactions from a common α,β-epoxy ester precursor.

A mild and inexpensive Ti(O i -Pr) 4 -mediated aminolysis of 2,3-epoxy amides has been developed. The reaction proceeds with excellent regioselectivity, regardless of the steric hindrance of the substituents on the heterocyclic ring, providing vicinal amino alcohols that are very suitable for synthetic applications.

A study on the addition of boron enolates of methyl ketones to trans α,β-epoxy aldehydes is reported. The reaction proceeds with an excellent anti stereoselectivity, consistent with the Felkin–Ahn model, toward the synthesis of hydroxylated compounds with defined stereochemistry.

A study of the organometallic addition to α,β-epoxy aldehydes in “non-chelation controlled” conditions is reported. The conditions able to give the best stereoselectivities are used to prepare the Abbott amino diol. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

An one-pot procedure for the synthesis of diprotected amino alcohols from 1,2-trans-substituted vinyl aziridines is studied.

The Lewis acid-catalyzed regioselective azidolysis of 2,3-three membered heterocyclic amines has been investigated. The results obtained demonstrated that using TMSN3 as a source of azide, the appropriate choice of Lewis acid allowed to obtain different regio- and stereocontrolled precursors of aminoalcoholic and triaminic sequences. Considering the occurrence of these moieties in the structure of many biologically active compounds, the present methodologies could represent a powerful tool in organic synthesis for the preparation of interesting molecules.

‘One pot’ organometallic addition and subsequent ring opening of α,β-aziridine aldehydes is reported to afford anti–syn 3-bromo-1,2-amino alcohols in high chemical yield and stereoselectivity. The sequence allows the stereoselective preparation of syn 1,2-amino alcohols.

The results obtained in the MgBr2-mediated opening of 2,3-bifunctionalized epoxides are reported. The studies showed that the chelation control of MgBr2 between different functionalities can in some cases be selective.

Dihydrofuran derivatives were obtained by a simple one-step procedure involving an easy epoxidation of 2-alkenyl-1,3-dicarbonyl compounds by dimethyldioxirane prepared in situ and a subsequent cyclisation under the same basic reaction conditions.

Selective ring opening and subsequent organometallic addition to α,β-epoxy aldehydes is found to afford anti-syn 3-bromo-1,2-diols in high stereo and chemical yield. This sequence is utilized for the enantioselective synthesis of (2S,3R,4R)-2-amino-1-cyclohexyl-6-methylheptane-3,4-diol (an isomer of the Abbott amino diol).

An easy and high yielding transformation of epoxyketones and phenyl substituted epoxides to trans olefins in a convergent diastereoselective process is reported. The method was applied to the selective C-25 hydroxy-functionalisation of 3-keto-Δ4-cholestan-3-one, a key intermediate for the synthesis of C-25 hydroxy vitamin D3.

A simple one pot procedure for the selective transformation of cyclic enones into α-halo-α,β-enones is reported using dimethyldioxirane and metal halides/Amberlyst 15. The method appears particulary appealing for the preparation of labelled molecules for use with the CMIA techinique.

Chiral 3-substituted N-Boc-2,3-aziridino alcohols are opened in a regio and stereoselective fashion by MgBr 2 ; the obtained 3-bromo derivatives can be reduced and deprotected under mild conditions to the corresponding 1,2-amino alcohols.

By means of semi-empirical quantum-mechanical computations the minimum energy conformations of several β-substituted carbonyl compounds have been examined. On the basis of a unified model with different β-substituents, two of the possible six conformers are found to be the most probable as reactant-like transition state structures, in a non-chelating nucleophilic addition, offering the same π face of the carbonyl group. The applicability of a single model for tsuch reaction has been examined. The conformational models proposed well correlate the diastereoselection of the experimental reactions for most of the cases examined.

Regio and stereoselective opening of three membered rings by metal halides was utilized for the enantioselective synthesis of (2 S ,3 R )-3-amino-2-hydroxydecanoic acid and (3 R )-3-aminodecanoic acid.

A recently reported study on the azidolysis of vinyl epoxides is extended to analogous N-protected aziridines (I) to produce azides (II), accompanied by low amounts of azides (III).

3-Substituted N-Ethoxycarbonyl aziridine-2-carboxylates are opened in a regio and stereoselective fashion whether in C-2 position by NaX (X = 1, Br) or in C-3 by MgBr 2

a novel synthesis of C 1 C 10 fragment of Nystatin A 1 was accomplished: the synthetic sequence utilized, as chiral building block, a protected syn 1,3 polyol previously obtained by chemoenzymatic route. The final fully protected fragment was then transformed to a known lactone in order to demonstrate the correct relative and absolute configuration.

α,β-Epoxy esters are opened by NaX (X = I, Br) in a regio and stereoselective fashion to β-hydroxy-α-halo esters, which represent suitable precursors of syn α-amino-β-hydroxy esters and β-hydroxy esters.

The enantio and stereoselective synthesis of (5R, 6S)-6-acetoxy-hexadecanolide is described via chemo, regio and stereoselective opening with LiI of a chiral epoxy alcohol precursor.

A novel simple protocol allows the preparation of highly functionalized vicinal amino alcohols under mild conditions.

Harmful or carcinogenic solvents such as CH2Cl2, Et2O, MeCN or acetone can be successfully replaced by the more eco-friendly medium dimethylcarbonate in nucleophilic ring-opening reactions of oxiranes and aziridines.

an aldol-reduction one-pot sequence allows syn-syn polyketide fragments such as 7 to be obtained enantio and diastereoselectively. Enol diisopinocampheylborinate is able to influence both the aldol and the subsequent reduction with NaBH4, via a chelate chair like intermediate.

Recent developments in the regio-, chemo- and stereoselective oxirane cleavage by new halogenating reagents allow obtention of various vicinal halohydrins. Also, epoxy alcohols and other functionalized oxiranes can be conveniently converted into the corresponding halohydrins. Some of the new methodologies have been successfully applied to the preparation of optically active fragments toward the synthesis to more complex molecules and natural products