Cardiovascular diagnostic methods in patients with diabetes mellitus. A review.

Cardiovascular diseases are the most common cause of mortality in the world. Currently, type 2 diabetes mellitus (T2DM) is one of the main risk factors for major adverse cardiovascular events. T2DM patients have a four-fold higher risk of developing heart failure and 10 to 12 times higher mortality.

Influence of Pore Size in Benzoin Condensation of Furfural Using Heterogenized Benzimidazole Organocatalysts.

A designed N-heterocyclic carbene (NHC) catalyst was covalently anchored on a range of mesoporous and hierarchical supports, to study the influence of pore size in the benzoin condensation of furfural. The structural and spectroscopic characteristics of the anchored catalysts were investigated, also with the help of molecular dynamics simulations, in order to rationalize the degree of stability and recyclability of the heterogenized organocatalysts. Quantitative yields (99 %) and complete recyclability were maintained after several cycles, vindicating the design rationale.

Studying the reactivity of alkyl substituted BODIPYs: first enantioselective addition of BODIPY to MBH carbonates.

The first enantioselective addition of alkyl BODIPYs to Morita-Baylis-Hillman (MBH) carbonates is reported. This is the first reported enantioselective methodology using the methylene position of BODIPYs as a nucleophile. The reaction is efficiently catalyzed by cinchona alkaloids, achieving high enantioselectivities and total diastereoselectivity.

Synthesis, Photophysics, and Solvatochromic Studies of an Aggregated-Induced-Emission Luminogen Useful in Bioimaging.

Biological samples are a complex and heterogeneous matrix where different macromolecules with different physicochemical parameters cohabit in reduced spaces. The introduction of fluorophores into these samples, such as in the interior of cells, can produce changes in the fluorescence emission properties of these dyes, caused by the specific physicochemical properties of cells. This effect can be especially intense with solvatofluorochromic dyes, where changes in the polarity environment surrounding the dye can drastically change the fluorescence emission.

Hybrid catalysts based on N-heterocyclic carbene anchored on hierarchical zeolites.

Hybrid materials have been synthesized by anchoring a N-heterocyclic carbene (NHC) precursor on different inorganic zeolitic supports with hierarchical porosity, in particular hierarchical HZSM-5 and SAPO-5. Hierarchical porous inorganic supports have been obtained both by top-down and bottom-up approaches and the role of hierarchical porosity has been evaluated. A detailed physico-chemical characterization has been performed on the organic-inorganic hybrids using a multi-technique approach (XRD, volumetric and thermogravimetric analysis, ssNMR and FTIR) in order to establish a structure-property relationship.

Proline bulky substituents consecutively act as steric hindrances and directing groups in a Michael/Conia-ene cascade reaction under synergistic catalysis.

In this study, we report a highly stereoselective and versatile synthesis of spiro pyrazolones, promising motifs that are being employed as pharmacophores. The new synthetic strategy merges organocatalysis and metal catalysis to create a synergistic catalysis using proline derivatives and Pd catalysts. This protocol is suitable for late-stage functionalization, which is very important in drug discovery.

Synergistic Catalysis: Highly Enantioselective Cascade Reaction for the Synthesis of Dihydroacridines.

The first stereoselective synthesis of dihydroacridines through synergistic catalysis, achieving the final target compounds with good to excellent yields and good to excellent enantioselectivities and diastereoselectivities, is reported. The synergistic approach consists in the activation of substituted quinolines with a Lewis acid catalyst that react in a cascade fashion with activated enals in the iminium form. Mechanistic calculations support a consecutive Michael-aldol reaction, followed by dehydration.

Synergistic formal ring contraction for the enantioselective synthesis of spiropyrazolones.

The rapid generation of molecular complexity from simple reactants is a key challenge in organic synthesis. Spiro compounds, underrepresented 3D motifs in chemical libraries, represent a challenge due to the creation of spiro quaternary carbon and the need to control the 3D shape in one step. Herein, we report the first ring contraction/formal [6 + 2] cycloaddition using synergistic Pd(0)/secondary amine catalysis, obtaining [5,5]-spiropyrazolone derivatives in excellent yields and stereoselectivities.

New development in the enantioselective synthesis of spiro compounds.

The enantioselective synthesis of spirocycles has long been pursued by organic chemists. Despite their unique 3D properties and presence in several natural products, the difficulty in their enantioselective synthesis makes them underrepresented in pharmaceutical libraries. Since the first pioneering reports of the enantioselective construction of spirosilanes by Tamao et al.

Synthetic applications of vinyl cyclopropane opening.

Vinyl cyclopropanes are amongst the most useful building blocks in organic synthesis. Their easy opening and capacity to generate dipoles have been exploited for the synthesis of cyclopentanes with good yields and sometimes excellent stereoselectivities. In this review we give an overview of their applications, focusing on the present century.

Synergistic Catalysis: Enantioselective Ring Expansion of Vinyl Cyclopropanes Combining Four Catalytic Cycles for the Synthesis of Highly Substituted Spirocyclopentanes Bearing up to Four Stereocenters.

A double synergistic cascade reaction is reported, combining transition metal and amine catalysis. The reaction between vinyl cyclopropanes and enals renders the final cyclopentane derivatives in excellent yields and stereoselectivities.

Enantioselective Organocatalytic Cyclopropanation of Enals Using Benzyl Chlorides.

Herein, we describe the first enantioselective cyclopropanation of enals using benzyl chlorides as bifunctional (nucleophilic and electrophilic) reagents. The reaction is simply catalyzed by chiral secondary amines to afford the formyl cyclopropane derivatives in good yields with moderate to excellent stereoselectivities.

Synergistic catalysis: -cyclopropanation of benzoxazoles.

In the present paper we report our latest efforts in pushing the boundaries of synergistic catalysis. We propose the use of 3 different catalytic cycles working in concert for the formation of cyclopropane derivatives of benzoxazoles with excellent stereoselectivities. This is the proof of concept that synergistic catalysis could be successfully used in cascade reactions.

Acetaldehyde: A Small Organic Molecule with Big Impact on Organocatalytic Reactions.

Stereocontrolled formation of carbon-carbon and carbon-heteroatom bonds through asymmetric organocatalysis is a formidable challenge for modern synthetic chemistry. Among the most significant contributions to this field are the transformations involving the use of acetaldehyde or α-heteroatom-substituted acetaldehydes for constructing valuable synthons (e.g.

Expanding the scope of Metal-Free enantioselective allylic substitutions: Anthrones.

The highly enantioselective asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates with anthrones is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and excellent enantioselectivities.

Highly diastereoselective synthesis of spiropyrazolones.

We report a highly diastereoselective synthesis of spiropyrazolones catalyzed by secondary amines. The reported Michael-Aldol cascade reaction affords the desired spiropyrazolones bearing four chiral centers as a single diastereomer in excellent yields.

Synergistic catalysis: enantioselective addition of alkylbenzoxazoles to enals.

A novel catalytic enantioselective methodology based on synergistic catalysis is reported. The strategy involves: 1) the metal-Lewis-acid activation of alkylazaarenes, and 2) the secondary-amine activation of enals. Consequently, highly functionalized chiral alkylazaarenes were obtained in good yields and with reasonable stereoselectivity.

Synergistic catalysis: highly diastereoselective benzoxazole addition to Morita-Baylis-Hillman carbonates.

An expedited method has been developed for the diastereoselective synthesis of highly functionalized alkyl-azaarene systems with good yields and high diastereoselectivities (>15 : 1 dr). The methodology includes a synergistic catalysis event involving organometallic (10 mol% AgOAc) activation of an alkyl azaarene and Lewis base (10 mol% DABCO) activation of a Morita-Baylis-Hillman carbonate. The structure and relative configuration of a representative product were confirmed by X-ray analysis.

Enantioselective methodologies using N-carbamoyl-imines.

Nucleophilic addition to carbon-nitrogen double bonds (imines) represents one of the most common strategies for the synthesis of amine derivatives. In order to circumvent the problem associated with low reactivity of imines in nucleophilic addition, various imines with electron-withdrawing groups at nitrogen have been studied, and many of them were successfully applied in asymmetric methodologies. Especially N-carbamoyl imines were found to be useful in the enantioselective synthesis of various organic compounds, due to their increased reactivity toward nucleophiles as well as limited difficulties connected with the removal of the carbamoyl moiety in target molecules.

First one-pot organocatalytic synthesis of α-methylene-γ-lactones.

All in one pot: an organocatalytic highly enantioselective synthesis of α-methylene-γ-lactones has been reported. The reaction between protected 2-hydroxymalonates and MBH carbonates is simply catalysed by chiral Lewis bases affording after acid treatment the corresponding lactones in excellent yields and enantioselectivities.

Organocatalytic enantioselective pyrazol-3-one addition to maleimides: reactivity and stereochemical course.

The enantioselective synthesis of pyrazol-3-ones has not been extensively studied in organic synthesis. Here in we report the first asymmetric addition of pyrazolones to maleimides catalyzed by bifunctional thiourea catalysts.

Enantioselective organocatalytic oxyamination of unprotected 3-substituted oxindoles.

An enantioselective α-oxyamination of unprotected 3-substituted oxindoles with nitrosobenzene catalyzed by tertiary amine-thiourea bifunctional organocatalysts has been developed and affords the corresponding 3-amino-2-oxindole derivatives in good yields and with moderate to excellent enantioselectivities (up to > 99.9 : 0.1 er when the product is isolated by direct filtration from the reaction mixture).

Enantioselective methodologies for the synthesis of spiro compounds.

The enantioselective synthesis of spirocycles has been a long time pursued dream for organic chemists. Since the first pioneering efforts of Tamao and coworkers in the enantioselective construction of spirosilanes, many efforts have been devoted to the development of new and promising asymmetric methodologies. Remarkably, with the advent of organocatalysis the number of methodologies has been highly increased.

Enantioselective organocatalytic asymmetric allylic alkylation. Bis(phenylsulfonyl)methane addition to MBH carbonates.

The highly enantioselective asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates with bis(phenylsulfonyl)methane is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and enantioselectivities.