Mild and General Protocol for Selective Deacetylation of Acetyl/Benzoyl-Protected Carbohydrates.

Herein, we report a mild and general protocol for chemoselective deacetylation of mixed acetyl- and benzoyl-protected carbohydrates under mild acidic conditions. The protocol allows quick access to partially protected carbohydrates, which serve as versatile synthetic intermediates during the total synthesis of various mono- and oligosaccharide targets. The applicability of the developed protocol was successfully demonstrated on a range of carbohydrate substrates of various configurations and substitution patterns featuring functionalized aliphatic and aromatic aglycones. The protocol has shown excellent compatibility with the widely used O-anomeric protecting groups, prespacer aglycones, and thioglycoside glycosyl donors.

Asymmetric synthesis of unnatural α-amino acids through photoredox-mediated C-O bond activation of aliphatic alcohols.

Unnatural α-amino acids constitute a fundamental class of biologically relevant compounds. However, despite the interest in these motifs, synthetic strategies have traditionally employed polar retrosynthetic disconnections. These methods typically entail the use of stoichiometric amounts of toxic and highly sensitive reagents, thereby limiting the substrate scope and practicality for scale up. In this work, an efficient protocol for the asymmetric synthesis of unnatural α-amino acids is realized through photoredox-mediated C-O bond activation in oxalate esters of aliphatic alcohols as radical precursors. The developed system uses a chiral glyoxylate-derived N-sulfinyl imine as the radical acceptor and allows facile access to a range of functionalized unnatural α-amino acids through an atom-economical redox-neutral process with CO2 as the only stoichiometric byproduct.

General Approach to Amides through Decarboxylative Radical Cross-Coupling of Carboxylic Acids and Isocyanides.

Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications.

Construction of Phenanthridinone Skeletons through Palladium-Catalyzed Annulation.

Herein, a straightforward synthetic approach for the construction of phenanthridin-6(5H)-one skeletons is disclosed. The developed protocol relies on palladium catalysis, providing controlled access to a range of functionalized phenanthridin-6(5H)-ones in 59-88% yields. Furthermore, plausible reaction pathways are proposed based on mechanistic experiments.

Sweetened Alkylated Verdazyls Effectively Kill Cancer Cells under Light Irradiation.

The development of novel photo-dynamic therapy (PDT) agents enabling to treat the oxygen-deficient tumors is the emerging tasks for the modern medicinal chemistry. Herein, we describe the design and preparation of water-soluble agents for PDT which generate active radical species upon light irradiation. Two conjugates of carbohydrates with 1,2,4,6-substituted-1,4-dihydro-1,2,4,5-tetrazin-3(2H)-ones (AlkVZs) demonstrated high oxygen-independent cytotoxicity on PC-3 and Jurkat cancer cells under light irradiation combining with low toxicity in the dark. The efficacy of prepared compounds was estimated using MTT and Alamar Blue tests as well as microscopic dead/live colored images and flow cytometry. The analysis of obtained results reveals the influence of sugar moiety on the activity of AlkVZs. We believe that obtained compounds have high potency as platform for design of new agents for photo-dynamic therapy.

Task measuring implicit attractiveness as a function of skin tone and facial features: a failed replication.

In two studies, participants completed an implicit attractiveness task with faces as primes varying on (a) facial features from Afrocentric to Eurocentric and (b) skin tone from dark to light, and target pictures of environmental scenes varying in attractiveness. On each trial, participants were briefly primed with a face. Next, they categorized a target picture as either attractive or unattractive as quickly as possible. In addition, in Study 2, participants rated the same faces on an attractiveness scale. While results of Study 1 showed that when faces were medium in skin tone, participants were more accurate when primed with a Eurocentric face responding to attractive targets, but also more accurate when primed with an Afrocentric face responding to unattractive targets, a more powerful Study 2 failed to replicate this effect. There was no relationship between participants' explicit ratings of attractiveness and accuracy rates in the implicit attractiveness task.

Scalable total synthesis of natural vanillin-derived glucoside ω-esters.

The first total synthesis of vanilloloside, calleryanin, and a series of naturally occurring ω-esters of vanilloloside was realized through direct glycosylation of vanillin-based aglycones or late-stage derivatization of vanilloloside. All aglycones and their fragments were synthesized from vanillin as the sole aromatic precursor. Subsequently, these intermediates were used to construct various vanillin-derived glucoside ω-esters using a mild acidic deacetylation as the key synthetic step, providing the final products in the total yields of 10-50% and general purity of >95%. Additionally, the first operationally simple and sustainable synthesis of litseafoloside B was realized on large scale, avoiding the use of toxic solvents and reagents, providing an attractive alternative to isolation of this and other similar compounds from plant sources.

Exploiting photoredox catalysis for carbohydrate modification through C-H and C-C bond activation.

Photoredox catalysis has recently emerged as a powerful synthetic platform for accessing complex chemical structures through non-traditional bond disconnection strategies that proceed through free-radical intermediates. Such synthetic strategies have been used for a range of organic transformations; however, in carbohydrate chemistry they have primarily been applied to the generation of oxocarbenium ion intermediates in the ubiquitous glycosylation reaction. In this Review, we present more intricate light-induced synthetic strategies to modify native carbohydrates through homolytic C-H and C-C bond cleavage. These strategies allow access to glycans and glycoconjugates with profoundly altered carbohydrate skeletons, which are challenging to obtain through conventional synthetic means. Carbohydrate derivatives with such structural motifs represent a broad class of natural products integral to numerous biochemical processes and can be found in active pharmaceutical substances. Here we present progress made in C-H and C-C bond activation of carbohydrates through photoredox catalysis, focusing on the operational mechanisms and the scope of the described methodologies.

Stereoselective synthesis of unnatural α-amino acid derivatives through photoredox catalysis.

A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids. The developed protocol allows the use of ubiquitous carboxylic acids as radical precursors without prior derivatization. The protocol utilizes near-stoichiometric amounts of the imine and the acid radical precursor in combination with a catalytic amount of an organic acridinium-based photocatalyst. Alternative mechanisms for the developed transformation are discussed and corroborated by experimental and computational studies.

What Drives Racial Attitudes in Elementary School Children: Skin Tone, Facial Physiognomy, or Both?

This work examines whether racial attitudes-when measured by both explicit and implicit measures- are driven primarily by skin tone, facial physiognomy, or both in 5 to 12-year-old children. Participants evaluated faces varying in skin tone (from dark to light) and facial physiognomy (from Afrocentric to Eurocentric). In an explicit task, children rated how much they liked each face. In an implicit task, participants completed a child-friendly version of the Affect Misattribution Procedure, where they rated a Chinese character as "good" or "bad" following a racial prime. Results suggest that pro-White attitudes (especially those measured by the explicit task) are driven by both factors, vary by perceivers' race, and are present in both White and non-White children, though skin tone exerts a larger influence than other features, at least in explicit evaluations. Our results also raise the possibility that pro-White biases might be more internalized by non-White children in the American South.

Alcohol Priming and Attribution of Blame in an Acquaintance Rape Vignette.

Research on nonpharmacological effects of alcohol shows that exposure to alcohol-related cues (i.e., alcohol priming) can increase behaviors associated with actual alcohol consumption. Attributions of responsibility to female victims in sexual assault scenarios are affected by whether or not alcohol was consumed by a victim and/or perpetrator. Victims often receive higher levels of blame if they consume alcohol prior to the assault. This work extends the research on nonpharmacological effects of alcohol into a novel domain of blame attribution toward rape victims. In two studies, participants in lab settings (Study 1; N = 184) and online (Study 2; N = 421) were primed with alcohol or neutral beverage advertisements as part of a purportedly separate ad-rating task and then were presented with a vignette depicting an acquaintance rape where the characters consumed beer or soda. Participants subsequently completed a questionnaire assessing victim blame and perpetrator blame. Across both studies, participants blamed the victim most when they were exposed to both contextual (story) and noncontextual (ads) alcohol cues; this effect was especially prominent in males in Study 1. Findings for perpetrator blame were inconsistent across studies. Implications of nonpharmacological effects of alcohol on blame attribution toward rape victims are discussed in the context of courtroom situations and bystander intervention.

Divergent Synthesis of Natural Benzyl Salicylate and Benzyl Gentisate Glucosides.

Herein is reported the first total synthesis of benzyl salicylate and benzyl gentisate glucosides present in various plant species, in particular the Salix genus, such as Populus balsamifera and P. trichocarpa. The method permits the synthesis of several natural phenolic acid derivatives and their glucosides starting from salicylic or gentisic acid. The divergent approach afforded access to three different acetylated glucosides from a common synthetic intermediate. The key step in the total synthesis of naturally occurring glycosides-the selective deacetylation of the sugar moiety-was achieved in the presence of a labile benzyl ester group by employing mild deacetylation conditions. The protocol permitted synthesis of trichocarpine (4 steps, 40% overall yield), isotrichocarpine (3 steps, 51% overall yield), trichoside (6 steps, 40% overall yield), and deoxytrichocarpine (3 steps, 42% overall yield) for the first time (>95% purity). Also, the optimized mild deacetylation conditions allowed synthesis of 2-O-acetylated derivatives of all four glycosides (5-17% overall yield, 90-95% purity), which are rare plant metabolites.

Synthesis of Salicaceae Acetyl Salicins Using Selective Deacetylation and Acetyl Group Migration.

In the present work, the synthesis of acetylated salicins, which occur naturally in many Salicaceae species, is reported. The preparation of 2-O-acetylsalicin, 2-O-acetylchlorosalicin, and 2-O-acetylethylsalicin from peracetylated bromosalicin with selective acid-catalyzed deacetylation and one-pot nucleophilic substitution of bromine as the key steps is described. The base-catalyzed O-2 → O-6 acetyl migration afforded 6-O-acetylsalicin derivatives in good yields. Thus, the first synthesis of 6-O-acetylsalicin (fragilin) using acetyl group migration is reported as well as the synthesis of 6-O-acetylchlorosalicin and 6-O-acetylethylsalicin. The NaOMe-catalyzed deacetylation of acetylated glycosides gave salicin, chlorosalicin, and ethylsalicin recently reported from Alangium chinense.

Catalyst-free regioselective acetylation of primary hydroxy groups in partially protected and unprotected thioglycosides with acetic acid.

Highly regioselective acetylation of primary hydroxy groups in thioglycoside derivatives with gluco- and galacto-configurations was achieved by treatment with aqueous or anhydrous acetic acid (60-100% AcOH) at elevated temperatures (80-118 °C), avoiding complex, costly and time-consuming manipulations with protective groups. Acetylation of both 4,6-O-benzylidene acetals and the corresponding diols as well as the unprotected tetraol with AcOH was shown to lead selectively to formation of 6-O-acetyl derivatives. For example, the treatment of phenyl 1-thio-ß-d-glucopyranoside with anhydrous AcOH at 80 °C for 24 h gave the corresponding 6-O-acetylated derivative in 47% yield (71% based on the reacted starting material) and unreacted starting tetraol in 34% yield, which can easily be recovered by silica gel chromatography and reused in further acetylation.

The role of feature-based discrimination in driving health disparities among Black Americans.

Objective: A growing body of research finds that darker skin tone is often associated with poorer physical and mental health in Blacks. However, the psychosocial mechanisms underlying the skin tone-health link remain elusive. The present study seeks to address this knowledge gap by investigating the direct and indirect (through perceived discrimination, socioeconomic status, and self-esteem) effects of skin tone on self-reported physical and mental health.Design: An urban sample of 130 Blacks aged 35 and above completed a self-administered computerized survey as a part of larger cross-sectional study.Results: Self-esteem played a particularly important role in mediating the associations between skin tone and self-reported physical and mental health. This suggests that self-esteem could be a point of intervention to help Blacks with darker skin tone achieve better health.Conclusion: The present study highlights the important role feature-based discrimination plays in determining mental and physical health outcomes among Blacks.

Black American College Students Report Higher Memory of Love for Mothers in Childhood Than White Students.

Cultural differences between Black and White individuals in the South are connected to the inequitable history of the United States. We wondered if these cultural differences would translate to a particularly precious aspect of life: memories of love felt in childhood toward one's parents. Some past studies have shown that Whites score higher on parental attachment measures to parents than Blacks, while other studies show no significant differences. However, no previous study has ever measured memory of feelings of love in relation to differences between ethnicities. In this study, Black (n = 124) and White (n = 125) undergraduates self-reported the strength and frequency of their past feelings of love toward their mother and father in first, sixth, and ninth grade as well as their current feelings of love. Results suggested that Black students reported feeling more love for their mothers in first, sixth, and ninth grades compared to White students. These findings were not explained when we statistically adjusted for age, gender, socioeconomic status, education levels, income, number of years spent living with mother or father, stress, or personality. Therefore, this relationship may be explained by unmeasured or unmeasurable cultural differences. The direction of this effect was in the opposite direction from what we expected based on past attachment research. Given the inequities in U.S. history and the current discussions around ethnicity and race in the United States, the finding that Blacks reported higher remembered feelings of love for their mothers in childhood is intriguing and worthy of dissemination and discussion.

Janus glycosides of next generation: Synthesis of 4-(3-chloropropoxy)phenyl and 4-(3-azidopropoxy)phenyl glycosides.

Efficient procedures for the preparative synthesis of per-O-acyl derivatives of 4-(3-chloropropoxy)phenyl (CPP) glycosides of a series of common mono- and disaccharides (d-glucose, d-galactose, d-mannose, l-rhamnose, d-arabinofuranose, d-glucosamine, lactose) are described. The CPP glycosides obtained were transformed in almost quantitative yields to the corresponding unprotected 4-(3-azidopropoxy)phenyl (APP) glycosides, which could become next-generation Janus glycosides with cleavable spacer aglycon, ready for conjugation or further transformation.

The use of the novel glycosyl acceptor and supramer analysis in the synthesis of sialyl-α(2-3)-galactose building block.

A new glycosyl acceptor to be used in sialylation was designed as a 3-hydroxy derivative of 4-methoxyphenyl ß-d-galactopyranoside with 2-O-acetyl group and O-4 and O-6 protected as benzylidene acetal. Two alternative syntheses of this compound were compared. Sialylation of 3-OH group of the glycosyl acceptor with O-chloroacetylated N-trifluoroacetylneuraminic acid phenyl thioglycoside (NIS, TfOH, MeCN, MS 3 Å, -40 °C) was studied in a wide concentration range (5-150 mmol L-1). The outcome of sialylation generally followed the predictions of supramer analysis of solutions of sialyl donor in MeCN, which was performed by polarimetry and static light scattering and revealed two concentration ranges differing in solution structure and the structures of supramers of glycosyl donor. The optimized conditions of sialylation (C = 50 mmol L-1) were used to synthesize protected Neu-α(2-3)-Gal disaccharide (78%, α:ß = 13:1), which was then converted to sialyl-α(2-3)-galactose imidate building block useful for the synthesis of complex sialo-oligosaccharides.

A new look at acid catalyzed deacetylation of carbohydrates: A regioselective synthesis and reactivity of 2-O-acetyl aryl glycopyranosides.

In the present work we report that acetyl groups of per - acetylated aryl glycosides have different reactivity during the acidic deacetylation using HCl/EtOH in CHCl3, which leads to preferential deacetylation at O-3, O-4 and O-6. Thereby, the one-step preparation of 2-O-acetyl aryl glycosides with simple aglycon was accomplished for the first time. It was proved that the found reagent is to be general and unique for the preparation of series of 2-О-acetyl aryl glycosides. We have determined the influence of both carbohydrate moiety and the aglycon on the selectivity of deacetylation reaction by kinetic experiments. Using DFT/B3LYP/6-31G(d,p) and semi-empirical АМ1 methods we have found that the highest activation barrier is for 2-О-acetyl group. This completely explains the least reactivity of 2-О-acetyl group.

Attractiveness as a Function of Skin Tone and Facial Features: Evidence from Categorization Studies.

Participants rated the attractiveness and racial typicality of male faces varying in their facial features from Afrocentric to Eurocentric and in skin tone from dark to light in two experiments. Experiment 1 provided evidence that facial features and skin tone have an interactive effect on perceptions of attractiveness and mixed-race faces are perceived as more attractive than single-race faces. Experiment 2 further confirmed that faces with medium levels of skin tone and facial features are perceived as more attractive than faces with extreme levels of these factors. Black phenotypes (combinations of dark skin tone and Afrocentric facial features) were rated as more attractive than White phenotypes (combinations of light skin tone and Eurocentric facial features); ambiguous faces (combinations of Afrocentric and Eurocentric physiognomy) with medium levels of skin tone were rated as the most attractive in Experiment 2. Perceptions of attractiveness were relatively independent of racial categorization in both experiments.