Decarboxylative photoinduced ligand-to-metal charge transfer reaction: synthesis of 2-substituted chroman-4-ones.

In this manuscript, a photoinduced ligand-to-metal charge transfer (LMCT) approach, employing transition-metal-based photocatalysts, for the efficient alkylation of electron-poor olefin is described. The developed redox-neutral process benefits from mild reaction conditions and involves a wide range of chromone-3-carboxylic acids as well as nucleophiles amenable to selective C-H functionalization leading to the formation of 2-substituted chroman-4-one compounds with potential biological activity.

Visible Light Promoted [3+2]-Cycloaddition for the Synthesis of Cyclopenta[b]chromenocarbonitrile Derivatives.

In the manuscript, a novel method for the preparation of cyclopenta[b]chromenocarbonitrile derivatives via [3+2] cycloaddition reaction of substituted 3-cyanochromones and N-cyclopropyloamines initiated by visible light catalysis has been described. The reaction was performed in the presence of Eosin Y as a photocatalyst. The key parameters responsible for the success of the described strategy are visible light, a small amount of photoredox catalyst, an anhydrous solvent, and an inert atmosphere.

Synthesis of cyclopent-1-enecarbonitriles via a tandem Giese/HWE reaction initiated by visible light.

In the manuscript, a novel method for the preparation of cyclopent-1-enecarbonitriles via tandem Giese/HWE reaction initiated by visible light in the presence of fac-Ir(ppy)3 as a photocatyst has been described. The cascade reactivity combining radical and polar processes has proven applicable for a wide range of N-(acyloxy)phthalimides (which serve as precursors of the corresponding radicals) as well as diethyl (E)-(1-cyano-2-arylvinyl)phosphonates. The key parameters responsible for the success of the described strategy are: visible light, 1 mol% of photoredox catalyst, base, anhydrous solvent and inert atmosphere. The reaction results in new sp3-sp3 and sp2-sp2 carbon-carbon bonds formation under mild conditions.

Enantioselective, Decarboxylative (3+2)-Cycloaddition of Azomethine Ylides and Chromone-3-Carboxylic Acids.

Herein, we describe the synthesis of a variety of chiral hybrid pyrrolidine-chromanone polycyclic derivatives. A convenient (3+2)-annulation of azomethine ylides with chromone-3-carboxylic acid realized under Brønsted base catalysis produced highly functionalized products in high yields with good stereoselectivities through asymmetric, intermolecular, and decarboxylative (3+2)-cyclization.

Visible Light-Driven Reductive Azaarylation of Coumarin-3-carboxylic Acids.

In the manuscript, reductive and decarboxylative azaarylation of coumarin-3-carboxylic acids is described. It utilizes the photocatalytic activation of (cyano)azaarenes in the presence of fac-Ir(ppy)3 as a photocatalyst. The methodology is versatile and provides access to biologically relevant 4-substituted-chroman-2-ones. Visible light, photoredox catalyst, base, anhydrous solvent, and inert atmosphere constitute key parameters for the success of the described strategy. The developed methodology involves a wide range of coumarin-3-carboxylic acids as well as (cyano)azaarenes.

Doubly Decarboxylative Synthesis of 4-(Pyridylmethyl)chroman-2-ones and 2-(Pyridylmethyl)chroman-4-ones under Mild Reaction Conditions.

The doubly decarboxylative Michael-type addition of pyridylacetic acid to chromone-3-carboxylic acids or coumarin-3-carboxylic acids has been developed. This protocol has been realized under Brønsted base catalysis, providing biologically interesting 4-(pyridylmethyl)chroman-2-ones and 2-(pyridylmethyl)chroman-4-ones in good or very good yields. The decarboxylative reaction pathway has been confirmed by mechanistic studies. Moreover, attempts to develop an enantioselective variant of the cascade are also described.

Hydroxyl-group-activated azomethine ylides in organocatalytic H-bond-assisted 1,3-dipolar cycloadditions and beyond.

1,3-Dipolar cycloaddition constitutes a powerful means for the synthesis of five-membered heterocycles. Recently, the potential of this field of chemistry has been expanded by the employment of organocatalytic activation strategies. One group of substrates, namely imines derived from salicylaldehydes, is particularly useful. Additional activation via intramolecular H-bonding interactions offered by the presence of an ortho-hydroxyl phenolic group in their structure results in increased reactivity of these reactants. Furthermore, it can be utilized in subsequent reactions creating chemical and stereochemical diversity. This minireview provides a summary of the recent progress in this field of organocatalysis and indicates other important applications of hydroxyl-group-activated azomethine ylides in asymmetric organocatalysis.

Pyridylacetic acids and related systems as alkylheteroarene surrogates in asymmetric decarboxylative Michael addition.

In this manuscript, a novel method for the preparation of enantiomerically enriched pyridine derivatives has been described. It is based on the utilization of readily available 2-pyridylacetic acids as valuable synthons for the introduction of a pyridine ring in an asymmetric fashion. They have been used as pronucleophiles in asymmetric decarboxylative Michael addition to α,ß-unsaturated aldehydes. The synthesis based on iminium activation using a chiral aminocatalyst that controlled the stereochemical outcome of the transformation has been successfully accomplished.

Visible-light synthesis of 4-substituted-chroman-2-ones and 2-substituted-chroman-4-ones via doubly decarboxylative Giese reaction.

Doubly decarboxylative, photoredox synthesis of 4-substituted-chroman-2-ones and 2-substituted-chroman-4-ones is described. The reaction involves two independent decarboxylation processes: the first one initiating the cycle and the second completing the process. Visible light, photoredox catalyst, base, anhydrous solvent and inert atmosphere constitute the key parameters for the success of the developed transformation. The protocol proved applicable for coumarin-3-carboxylic acids and chromone-3-carboxylic acids as well as N-(acyloxy)phthalimide which served as precursors of the corresponding alkyl radicals.

Enantioselective Synthesis of Chromanones Bearing an α,α-Disubstituted α-Amino Acid Moiety via Decarboxylative Michael Reaction.

In this manuscript, a novel, decarboxylative Michael reaction between α-substituted azlactones and chromone-3-carboxylic acids is described. The reaction proceeds in a sequence Michael addition followed by decarboxylative deprotonation, and it results in the formation of chromanones bearing an azlactone structural unit. The possibility of transforming an azlactone moiety into a protected α,α-disubstituted α-amino acid derivative is also demonstrated.

Decarboxylative, trienamine mediated cycloaddition for the synthesis of 3,4-dihydrocoumarin derivatives.

In this Communication, a new approach for trienamine chemistry is described. It is based on the application of carboxylic-acid-activated dienophiles that undergo spontaneous decarboxylative protonation after the initial [4 + 2]-cycloaddition step. The utilization of such a novel cascade reaction for the synthesis of biologically relevant 3,4-dihydrocoumarins has been demonstrated. High levels of enantiocontrol and excellent yield of the cascade reaction have been achieved by the use of diphenylprolinol diphenylmethylsilyl ether.

The NOP-1 peptide derived from the central regulator of ethylene signaling EIN2 delays floral senescence in cut flowers.

The plant hormone ethylene was identified as important triggering factor and primary regulator of flower senescence in many species. Consequently, application of chemical inhibitors of ethylene biosynthesis and action is used to extend the longevity of ethylene-sensitive flowers. Here, we show that the peptide NOP-1, a biological derived from the nuclear localization signal of ethylene regulator EIN2 tightly binds to the ethylene receptor of carnation plants - a model to study flower senescence. When applied on cut flowers the peptide biological delays petal senescence similar to previously identified and currently used chemical inhibitors, but offers significant advances to these chemicals in biodegradability, sustainability and ecotoxicity. Our bioinformatic analysis of a wide range of ethylene receptors indicates complete sequence conservation of the anticipated NOP-1 binding site in flower species supporting a widespread use of the peptide on flowering ornamentals to delay senescence and decay in cut flowers. We anticipate our innovative approach to extend flower longevity by a new class of biomolecules such as peptides, peptide analogues and peptide mimetics will significantly advance our technological capability to delay flower senescence and expand vase-life of cut flowers in a sustainable and environmentally friendly manner.

Opposition to Inbreeding Between Close Kin Reflects Inclusive Fitness Costs.

Due to the intense selection pressure against inbreeding, humans are expected to possess psychological adaptations that regulate mate choice and avoid inbreeding. From a gene's-eye perspective, there is little difference in the evolutionary costs between situations where an individual him/herself is participating in inbreeding and inbreeding among other close relatives. The difference is merely quantitative, as fitness can be compromised via both routes. The question is whether humans are sensitive to the direct as well as indirect costs of inbreeding. Using responses from a large population-based sample (27,364 responses from 2,353 participants), we found that human motivations to avoid inbreeding closely track the theoretical costs of inbreeding as predicted by inclusive fitness theory. Participants were asked to select in a forced choice paradigm, which of two acts of inbreeding with actual family members they would want to avoid most. We found that the estimated fitness costs explained 83.6% of participant choices. Importantly, fitness costs explained choices also when the self was not involved. We conclude that humans intuit the indirect fitness costs of mating decisions made by close family members and that psychological inbreeding avoidance mechanisms extend beyond self-regulation.

Chiral Iminophosphoranes-An Emerging Class of Superbase Organocatalysts.

Chiral Brønsted base catalysis is a fascinating and highly explored field of research. For many years catalysts based on chincona alkaloid chiral scaffolds have constituted privileged systems widely employed in numerous base-promoted organic transformations. Recently, a novel group of chiral base catalysts has been successfully introduced. The application of organosuperbases, namely cyclopropenimines, guanidines, and iminophosphoranes, as chiral catalysts is receiving increasing attention. The aim of this Concept article is to summarize recent progress in the field of chiral iminophosphorane superbase organocatalysis. Catalysts design, different approaches to their synthesis, and applications in asymmetric synthesis are outlined and discussed in detail.

The self-regulation effect of fertility status on inbreeding aversion: when fertile, disgust increases more in response to descriptions of one's own than of others' inbreeding.

The ovulatory shift modulates emotions related to female sexuality. Because fertility status only affects the individual's own opportunity cost, the adaptive value of this shift is expected to stem from self-regulation. To test this assumption we asked women to contemplate various inbreeding descriptions: 1) they themselves having sex with male relatives; 2) their sister having sex with their common male relatives; and 3) an unrelated woman having sex with her male relatives (in 1, but not 2 and 3, negative fitness consequences are affected by the participant's fertility). We dichotomized the dependent variable disgust (ceiling vs. non-ceiling) and analyzed the interaction between fertility status and description type. The ovulatory shift was stronger in descriptions where they themselves were described as engaging in inbreeding. A smaller increase was also found in reactions to others engaging in inbreeding. We explain the latter effect as due to self-reflection.

Self-reported availability of kinship cues during childhood is associated with kin-directed behavior to parents in adulthood.

Reliable recognition of kin is an important factor in modulating kin-directed behaviors. For example, in selectively directing cooperative behavior to kin and diverting sexual interest away from them, kin first need to be recognized as such. Although an increasing number of studies have examined what information is employed in recognizing siblings and children, less is known about the information children employ in identifying their parents. In a web-based survey, we asked 702 Finnish undergraduate and graduate students to report the availability of a number of possible kinship cues during their childhood and youth. After factorization of the responses, we found that the reported amount of parental support, phenotypic similarity, and behavioral similarity generally predicted subjective certainty in relatedness and kin-directed behavior (i.e., cooperative behavior and inbreeding aversion) to parents in adulthood. Although the data suffer from their retrospective nature, the present study provides potentially useful information about kin-recognition of parents.

Growth performance and carcass characteristics of Improvac-treated male pigs compared with barrows.

The present study assessed the effects of using Improvac (Pfizer Animal Health, Germany) on growth performance and meat characteristics in cross-bred male pigs. In addition average daily weight gain of immunised and surgically castrated males was estimated in order to demonstrate differences in growing patterns in these two treatment groups. The study was carried out in two identical batches. Pigs within batches (n = 446) were allocated to two different treatment groups: immunisation (IM) versus surgical castration (CM). Within treatment groups pigs were randomly assigned to two different diets (low- and high-lysine diet) in order to examine interactions of growth performance and castration technique. Vaccination was performed on the day of entry to the fattening unit and four to six weeks prior to slaughter. At the second vaccination IM-pigs showed significantly lower body weights than the control group (p < 0.05) in both batches. Throughout the whole fattening period CM-pigs tended to have a higher feed intake than IM-pigs while IM-pigs had a significantly lower (better) feed conversion ratio than CM-pigs (p < 0.05).The different lysine content of the diets had no coherent effect on any of the growth performance parameters analysed. Immunised pigs of both feeding groups and in both batches showed a tendency towards a lower carcass weight, back fat values and dressing percentages than surgically castrated pigs.The castration technique had no significant effect on meat quality parameters such as drip loss, shear force or cooking loss while intramuscular fat content (IMF) in immunised pigs fed high-lysine diets (IM(high)) tended to be higher than IMF in immunised pigs fed low-lysine diets (IM(low)). This effect was not seen in surgical castrates in either batch. Immunisation against GnRH offers a good approach to produce taint-free pork while ensuring boar-like growth for a large part of the fattening period.

Enantioselective H-bond-directing approach for trienamine-mediated reactions in asymmetric synthesis.

Right direction: The presented enantioselective strategy for the preparation of diversely functionalized tetrahydroxanthones is based on a trienamine-mediated cycloaddition between 2,4-dieneals and activated chromones. It is possibile to control the stereochemical outcome of such reactions by employing an H-bond-directing aminocatalyst.

YMCA commit to quit: randomized trial outcomes.

BACKGROUND: Vigorous-intensity exercise has been shown to aid in smoking cessation, especially among women. In a previous trial, cognitive behavioral therapy (CBT) for smoking cessation plus regular vigorous aerobic exercise enhanced cessation rates, improved exercise capacity, and reduced weight gain compared to CBT plus equal contact time. PURPOSE: This study examined the effectiveness of this program adapted for and implemented in the YMCAs. DESIGN: An RCT comparing CBT + Exercise (Exercise) to CBT + Contact Control (Control). SETTING/PARTICIPANTS: Apparently healthy female smokers were recruited to four local YMCAs. INTERVENTION: YMCA staff members were trained to lead the manualized CBT smoking-cessation intervention and a standardized YMCA exercise program. MAIN OUTCOME MEASURES: Seven-day point prevalence and continuous abstinence. RESULTS: Participants (330 women, mean age=44 years) were randomized to the Exercise (n=166) or Control (n=164) group. Results revealed no differences in 7-day point prevalence (29.5% vs 29.9%) nor continuous abstinence (13.9% vs 14.0%) between the Exercise and Control groups, respectively, at end of treatment or at the 3-, 6-, and 12-month follow-up. An examination of the relationship between exercise dose and quit status at end of treatment revealed that over 12 weeks, the odds of being quit (7-day point prevalence) grew by 4.5% for each additional aerobic exercise session (OR=1.05, 95% CI=1.01, 1.08) and by 7.7% for each additional resistance training session (OR=1.08, 95% CI=1.02, 1.14). Analyses were conducted between August 19, 2010, and December 16, 2011. CONCLUSIONS: No differences were seen between groups in smoking outcomes. The association between greater exercise participation and higher odds of quitting within the exercise condition suggests that the lack of between-group differences might be a result of poor compliance with the exercise program. TRIAL REGISTRATION: This study is registered at clinicaltrials.govNCT01615380.

Synthesis and biological evaluation of α-methylidene-δ-lactones with 3,4-dihydrocoumarin skeleton.

A series of new 3-methylidenechroman-2-ones bearing various aromatic moieties and various substituents at position 4 were synthesized in a three step reaction sequence. Friedel-Crafts alkylation of phenols or naphthols using ethyl 3-methoxy-2-diethoxyphosphorylacrylate in the presence of trifluoromethanesulphonic acid gave 3-diethoxyphosphorylchromen-2-ones. These compounds were employed as Michael acceptors in the reaction with Grignard reagents to give adducts which were finally used as Horner-Wadsworth-Emmons reagents for the olefination of formaldehyde. All obtained 3-methylidenechroman-2-ones were tested against two human leukemia cell lines NALM-6 and HL-60 as well as MCF-7 breast cancer and HT-29 colon cancer adenocarcinomas. Several obtained methylidenechromanones displayed high cytotoxic activity with IC(50) values below 1 µM, mainly against leukemia and MCF-7 cell lines. Investigation of structure-activity relationships revealed that the presence of additional, ortho-fused benzene ring and n-butyl or i-propyl group in position 4 enhances the activity. Selected methylidenechromanones were also tested on normal human umbilical vein endothelial cells (HUVEC) and chromanone 14o was found to be eightfold more toxic against MCF-7 than normal cells. Furthermore, antimicrobial assays revealed that chromanone 14n is highly active and bactericidal at concentration equal to MIC or 2MIC against nosocomial and community-associated staphylococci (MRSA) which are resistant to most or all available therapeutic classes of antimicrobial drugs.