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.

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.

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., significant effort has been devoted towards the development of new promising asymmetric methodologies. Remarkably, with the advent of organocatalysis, particularly over six years, the reported methodologies for the synthesis of spirocycles have increased exponentially. The aim of this review is to summarize the latest trends and developments in the enantioselective synthesis of spirocompounds during these last six years.

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. In this article, we studied the photophysical behavior of a new dye and confirmed the aggregation-induced emission (AIE) phenomenon with different approaches, such as by using different solvent proportions, increasing the viscosity, forming micelles, and adding bovine serum albumin (BSA), through analysis of the absorption and steady-state and time-resolved fluorescence. Our results show the preferences of the dye for nonpolar media, exhibiting AIE under specific conditions through immobilization. Additionally, this approach offers the possibility of easily determining the critical micelle concentration (CMC). Finally, we studied the rate of spontaneous incorporation of the dye into cells by fluorescence lifetime imaging and observed the intracellular pattern produced by the AIE. Interestingly, different intracellular compartments present strong differences in fluorescence intensity and fluorescence lifetime. We used this difference to isolate different intracellular regions to selectively study these regions. Interestingly, the fluorescence lifetime shows a strong difference in different intracellular compartments, facilitating selective isolation for a detailed study of specific organelles.

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.

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., amino acid derivatives and hydroxycarbonyl). In this Minireview, versatile (enantioselective) organocatalytic transformations are discussed.

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.

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. The aim of this review is to cover enantioselective methods based on N-carbamoyl imines, focusing on synthetically useful protocols.

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.

Role of DISC1 interacting proteins in schizophrenia risk from genome-wide analysis of missense SNPs.

A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including schizophrenia, in a Scottish family. DISC1 is a hub protein of a network of protein-protein interactions involved in multiple developmental pathways within the brain. Gene set-based analysis has been proposed as an alternative to individual analysis of single nucleotide polymorphisms (SNPs) to get information from genome-wide association studies. In this work, we tested for an overrepresentation of the DISC1 interacting proteins within the top results of our ranked list of genes based on our previous genome-wide association study of missense SNPs in schizophrenia. Our data set consisted of 5100 common missense SNPs genotyped in 476 schizophrenic patients and 447 control subjects from Galicia, NW Spain. We used a modification of the Gene Set Enrichment Analysis adapted for SNPs, as implemented in the GenGen software. The analysis detected an overrepresentation of the DISC1 interacting proteins (permuted P-value=0.0158), indicative of the role of this gene set in schizophrenia risk. We identified seven leading-edge genes, MACF1, UTRN, DST, DISC1, KIF3A, SYNE1, and AKAP9, responsible for the overrepresentation. These genes are involved in neuronal cytoskeleton organization and intracellular transport through the microtubule cytoskeleton, suggesting that these processes may be impaired in schizophrenia.

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. The aim of this tutorial review is to summarize the last trends and developments reported in the literature in the enantioselective synthesis of spirocompounds.

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). The absolute configuration of the major enantiomers of the products has been established both by chemical correlation and by comparison between the theoretically calculated and the experimental ECD.

Insight in schizophrenia and risk of suicide: a systematic update.

BACKGROUND: Suicide has been shown to represent the major single cause of premature death among patients with schizophrenia spectrum disorders. Insight has been proposed to increase such risk. However, this subject has not been sufficiently investigated, and inconclusive results have been reported. OBJECTIVE: The objective of this study is to systematically examine the role of insight in the risk of suicide attempts and completed suicide among patients with schizophrenia and related disorders. METHOD: Articles assessing insight and suicidality in patients with schizophrenia spectrum disorders published between 1977 and 2010 were reviewed. A MEDLINE search strategy was used to identify studies using keywords. Application of meta-analytic techniques to selected studies was not possible because of important methodological differences between them. RESULTS: Fifteen studies met predetermined selection criteria. Ten failed to demonstrate a positive association between insight and risk for suicide. DISCUSSION: There is little evidence to support the suggestion that insight may represent a risk factor for suicide in patients with schizophrenia. If there is an association between such risk and insight, it appears to be mediated by other variables such as depression and, above all, hopelessness. Further studies with larger samples and longer follow-up periods in naturalistic conditions, in which insight should be evaluated from a multidimensional approach, are required to analyze this issue in depth, given the crucial implications that it may have on the development of a model for suicide prevention in schizophrenia.

Telepsychogeriatrics: a new horizon in the care of mental health problems in the elderly.

BACKGROUND: The use of telemedicine for the care of mental health problems has developed significantly over the last decade thanks to the emergence of a number of stable telepsychiatry programs in many countries. Parallel to this development, this care modality has also targeted specific populations with higher difficulty in gaining access to mental health services such as the elderly. Telepsychogeriatrics is expected to have an increasing role in providing care to geographically isolated rural communities, with a particular focus on long-term care facilities, in light of the high prevalence of psychiatric disorders in these centers and the lack of available specialized care. METHODS: A thorough search of the literature was conducted using Medline, Web of Science, and PsychINFO databases in order to gather available evidence on the applicability of telepsychiatry, specifically the use of videoconferencing for remote consultation, in the elderly population with mental disorders. A succinct description of the selected studies is given along with a general reflection on the state-of-the-art in the field of psychogeriatric clinical practice and research. RESULTS: Research on the use of telemedicine in this age group has taken into account their special characteristics, and has focused on demonstrating its applicability, the acceptance and satisfaction of elderly users and their healthcare providers, the possibility of carrying out cognitive and diagnostic assessments, and the efficiency of these programs. CONCLUSIONS: Despite limited experience, telepsychogeriatrics appears to be a viable option, well accepted by patients, including those having dementia. More systematized studies are needed in this new field based on larger sample sizes, including comparison with traditional consultations and assessment of the clinical outcomes.

No evidence that major mtDNA European haplogroups confer risk to schizophrenia.

Previous studies suggest that genetic factors could be involved in mitochondrial dysfunction observed in schizophrenia (SZ), some of them claiming a role of mtDNA common variants (mtSNPs) and/or haplogroups (hgs) in developing this disorder. These studies, however, have mainly been undertaken on relatively small cohorts of patients and control individuals and most have not yet been replicated. To further analyze the role of mtSNPs in SZ risk, we have carried out the largest genotyping effort to date using two Spanish case-control samples comprising a total of 942 schizophrenic patients and 1,231 unrelated controls: 454 patients and 616 controls from Santiago de Compostela (Galicia) and 488 patients and 615 controls from Reus (Catalonia). A set of 25 mtSNPs representing main branches of the European mtDNA phylogeny were genotyped in the Galician cohort and a subset of 16 out of these 25 mtSNPs was genotyped in the Catalan cohort. These 16 common variants characterize the most common European branches of the mtDNA phylogeny. We did not observe any positive association of mtSNPs and hgs with SZ. We discuss several deficiencies of previous studies that might explain the false positive nature of previous findings, including the confounding effect of population sub-structure and deficient statistical methodologies. It is unlikely that mtSNPs defining the most common European mtDNA haplogroups are related to SZ.

Enantioselective organocatalytic synthesis of fluorinated molecules.

The enantioselective synthesis of fluorinated molecules has drawn much attention within the chemical community due to its unique stereoelectronic properties. The main aim of this review is to cover the most important organocatalytic enantioselective methodologies to obtain them. The review is divided into three parts: first, the direct introduction of a fluorine atom studied in the early 2000s. Second, the later use of Michael reactions to introduce fluorine-containing synthons. Finally, the simultaneously-developed trifluoromethylation reactions, giving the catalysts, mechanisms and reagents that have been used.

Catalytic asymmetric aziridination of α,ß-unsaturated aldehydes.

The development, scope, and application of the highly enantioselective organocatalytic aziridination of α,ß-unsaturated aldehydes is presented. The aminocatalytic azirdination of α,ß-unsaturated aldehydes enables the asymmetric formation of ß-formyl aziridines with up to >19:1 d.r. and 99% ee. The aminocatalytic aziridination of α-monosubstituted enals gives access to terminal α-substituted-α-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted α,ß-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure ß-formyl-functionalized aziridine products (99% ee). A highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis (AHCC) is also disclosed. This one-pot three-component co-catalytic transformation between α,ß-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy-protected ß-amino acid esters with ee values ranging from 92-99%. The mechanisms and stereochemistry of all these catalytic transformations are also discussed.