Search

A highly diastereoselective, one-pot strategy for spirooxindoles bearing dihydrophenanthrenes from readily available isatins and p-quinone methides (p-QMs) has been disclosed. Here, a sequential umpolung process via [1,2]-phospha-Brook rearrangement followed by Lewis acid-mediated intramolecular cyclization was employed to furnish the desired spiro product. This protocol provides access to potential medicinally relevant varieties of spirooxindolyl dihydrophenanthrenes in good to excellent yields and diastereoselectivity (>20: 1). [ABSTRACT FROM AUTHOR]

Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of β‐carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of β‐carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo‐/enantio‐selective control, and good functional group tolerance, allowing access to a variety of valuable chiral β‐carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions. Moreover, the efficiency and practicality of this approach are demonstrated by the asymmetric synthesis of bioactive compounds and natural products. [ABSTRACT FROM AUTHOR]

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARb) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination--a cognitive function reliant on the hippocampus--with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions. [ABSTRACT FROM AUTHOR]

Canonical retinoid signaling via nuclear receptors and gene regulation is critical for the initiation of developmental processes such as cellular dierentiation, patterning and neurite outgrowth, but also mediates nerve regeneration and synaptic functions in adult nervous systems. In addition to canonical transcriptional regulation, retinoids also exert rapid eects, and there are now multiple lines of evidence supporting non-canonical retinoid actions outside of the nucleus, including in dendrites and axons. Together, canonical and noncanonical retinoid signaling provide the precise temporal and spatial control necessary to achieve the fine cellular coordination required for proper nervous system function. Here, we examine and discuss the evidence supporting non-canonical actions of retinoids in neural development and regeneration as well as synaptic function, including a review of the proposed molecular mechanisms involve. [ABSTRACT FROM AUTHOR]

Aims: To explore the experiences, and perceptions of nurses who are told to withhold clinical information from children diagnosed with serious illnesses., Design: An interpretative qualitative phenomenological design was used for the study. Sampling was purposive and data were collected using semi-structured interviews from nurses working in a paediatric setting within the preceding 5 years. Nurse-participants described their personal experiences of withholding situations ('non-disclosure directives'). Their accounts of specific examples of situations ('personal accounts') were extracted from the interview transcripts and analysed using inductive content analysis to identify patterns and concepts within the descriptions. Data management was supported using Dedoose., Setting: Nurse-participants were interviewed face-to face and online between November 2019 and December 2020., Participants: Twenty-six Australian nurses who have cared for seriously ill children within the preceding 5 years participated in the study., Results: Thirty-nine accounts of non-disclosure situations (personal accounts) were extracted from interview transcripts. Four types of non-disclosure were identified in the personal accounts: withholding information, temporary withholding, lying and combined withholding/lying. The inductive content analysis identified three key aspects of nurse-participants' accounts: beliefs and perceptions (about the child and parents), the nature of the experience and feelings about the experience., Discussion: Moral distress occurred when nurses' actions conflicted with their moral values in response to a non-disclosure directive, particularly when asked to directly lie to children. Nurses felt disempowered by the parent's authority and the institutional hierarchy that limited their ability to participate in discussions where a non-disclosure directive was given., Conclusion and Impact: Nurse-participants were afforded a platform for reflection which proved valuable in allowing them to process their experiences in a non-disclosure situation., Recommendations: Nurses directed to withhold medical information from children should be afforded opportunities for reflection to mitigate moral distress. Nurses should be included in the planning of ethically appropriate responses to withholding directives., (© 2024 John Wiley & Sons Ltd.)

In the gastropod mollusk Lymnaea stagnalis, insulin-like peptides in the central nervous system (CNS) control behavioral changes associated with associative learning. Insulin administration to the Lymnaea CNS enhances the synaptic plasticity involved in this type of learning, but it has remained unclear which molecules in the insulin response cascade are involved. Here, to advance a comprehensive analysis, we used two-dimensional electrophoresis and comparative quantitative mass spectrometry to perform a protein analysis investigating the CNS molecules that respond to insulin administration. Our results revealed increased phosphorylation of AKT and RICTOR in the PI3K/AKT/mTOR signaling cascade and cytoskeleton-related proteins. Although it was expected that the molecules in the PI3K/AKT/mTOR signaling cascade were phosphorylated by insulin administration, our findings confirmed the correlation between insulin-induced phosphorylation of cytoskeletonrelated proteins strongly involved in the synaptic changes and learning and memory mechanisms. These results contribute to elucidate the relationship between the insulin response and learning and memory mechanisms not only in Lymnaea but also in various invertebrates and vertebrates. [ABSTRACT FROM AUTHOR]

This report has realized the catalytic asymmetric [3+2] annulation of benzylideneindolinones with CF3‐containing isatin‐derived azomethine ylides for the first time, in which the organocatalysis has failed. In the presence of dinuclear zinc catalysts, a series of functionalized 2,3‐pyrrolidinyl dispirooxindoles have been synthesized in good yields with excellent stereoselectivity under mild reaction conditions. This protocol can be run on a gram scale and a possible catalytic mechanism is proposed. [ABSTRACT FROM AUTHOR]

The emergence of resistance against current antimalarial treatments has necessitated the need for the development of novel antimalarial chemotypes. Toward this goal, we recently optimised the antimalarial activity of the dihydroquinazolinone scaffold and showed it targeted PfATP4. Here, we deconstruct the lactam moiety of the tricyclic dihydroquinazolinone scaffold and investigate the structure-activity relationship of the truncated scaffold. It was shown that SAR between scaffolds was largely transferrable and generated analogues with potent asexual stage activity. Evaluation of the truncated analogues against PfATP4 mutant drug-resistant parasite strains and in assays measuring PfATP4-associated ATPase activity demonstrated retention of PfATP4 as the molecular target. Analogues exhibited activity against both male and female gametes and multidrug resistant parasites. Limited efficacy of analogues in a P. berghei asexual stage mouse model was attributed to their moderate metabolic stability and low aqueous stability. Further development is required to address these attributes toward the potential use of the dihydroquinazolinone class in a curative and transmission blocking combination antimalarial therapy., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Nervous system is one of the key adaptations underlying the evolutionary success of the majority of animal groups. Ctenophores (or comb jellies) are gelatinous marine invertebrates that were probably the first lineage to diverge from the rest of animals. Due to the key phylogenetic position and multiple unique adaptations, the noncentralized nervous system of comb jellies has been in the center of the debate around the origin of the nervous system in the animal kingdom and whether it happened only once or twice. Here, we discuss the latest findings in ctenophore neuroscience and multiple challenges on the way to build a clear evolutionary picture of the origin of the nervous system., (© 2024 The Authors. Evolution & Development published by Wiley Periodicals LLC.)

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold‐catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin‐derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram‐scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones. [ABSTRACT FROM AUTHOR]

The demand for new biomass‐derived fine and commodity chemicals propels the discovery of new methodologies and synthons. Whereas furfural and 5‐hydroxymethylfurfural are cornerstones of sustainable chemistry, 3‐acetamido‐5‐acetyl furan (3A5AF), an N‐rich furan obtained from chitin biomass, remains unexplored, due to the poor reactivity of the acetyl group relative to previous furanic aldehydes. Here we developed a reactive 3‐acetamido‐5‐furfuryl aldehyde (3A5F) and demonstrated the utility of this synthon as a source of bio‐derived nitrogen‐rich heteroaromatics, carbocycles, and as a bioconjugation reagent. [ABSTRACT FROM AUTHOR]

A simple, facile, and highly efficient approach has been unfolded for the syntheses of β‐carboline tethered imidazole derivatives. This expeditious catalyst‐free strategy proceeds through the assembly of 1‐formyl‐9H‐β‐carbolines, glyoxal derivatives and ammonium acetate via the formation of concomitant four C−N bonds in a one‐pot operation. The current approach has various advantages, including multicomponent nature, simple reaction conditions, short reaction time, broad substrate scope, and high product yield. Importantly, the β‐carboline tethered imidazole derivatives displayed excellent photophysical properties with quantum yield up to 90%. [ABSTRACT FROM AUTHOR]

Herein, we have disclosed pentafluorophenol as an operative catalyst for synthesizing (spirocyclic) tetrahydro‐β‐carbolines via the Pictet‐Spengler reaction. This straightforward catalytic protocol works under mild conditions resulting indole alkaloids in excellent yield with remarkable functional group tolerance, including late‐stage modifications. This transformation demonstrates a practical and adaptable approach to produce a highly effective gram‐scale synthesis of the natural alkaloid Komavine and enables the synthesis of the commercial drug Tadalafil. [ABSTRACT FROM AUTHOR]

The pond snail Lymnaea stagnalis employs aerial respiration under hypoxia and can be operantly conditioned to reduce this behavior. When applied individually, a heat shock (30 °C for 1 h) and the flavonoid quercetin enhance long-term memory formation for the operant conditioning of aerial respiration. However, when snails are exposed to quercetin before the heat shock, long-term memory is no longer enhanced. This is because quercetin prevents the heat-induced upregulation of heat-shock proteins 70 and 40. When we tested the memory outcome of operant conditioning due to the simultaneous exposure to quercetin and 30 °C, we found that Lymnaea entered a quiescent survival state. The same behavioral response occurred when snails were simultaneously exposed to quercetin and pond water made hypoxic by bubbling nitrogen through it. Thus, in this study, we performed six experiments to propose a physiological explanation for that curious behavioral response. Our results suggest that bubbling nitrogen in pond water, heating pond water to 30 °C, and bubbling nitrogen in 30 °C pond water create a hypoxic environment, to which organisms may respond by upregulating the heat-shock protein system. On the other hand, when snails experience quercetin together with these hypoxic conditions, they can no longer express the physiological stress response evoked by heat or hypoxia. Thus, the quiescent survival state could be an emergency response to survive the hypoxic condition when the heat-shock proteins cannot be activated. [ABSTRACT FROM AUTHOR]

Development of antimalarial compounds into clinical candidates remains costly and arduous without detailed knowledge of the target. As resistance increases and treatment options at various stages of disease are limited, it is critical to identify multistage drug targets that are readily interrogated in biochemical assays. Whole-genome sequencing of 18 parasite clones evolved using thienopyrimidine compounds with submicromolar, rapid-killing, pan–life cycle antiparasitic activity showed that all had acquired mutations in the P. falciparum cytoplasmic isoleucyl tRNA synthetase (cIRS). Engineering two of the mutations into drug-naïve parasites recapitulated the resistance phenotype, and parasites with conditional knockdowns of cIRS became hypersensitive to two thienopyrimidines. Purified recombinant P. vivax cIRS inhibition, cross-resistance, and biochemical assays indicated a noncompetitive, allosteric binding site that is distinct from that of known cIRS inhibitors mupirocin and reveromycin A. Our data show that Plasmodium cIRS is an important chemically and genetically validated target for next-generation medicines for malaria. Antimalarial angle: The development of antimalarial compounds that target multiple stages of the Plasmodium falciparum life cycle remains a critical goal, especially in light of growing resistance to existing drugs. Istvan et al. exposed P. falciparum to thienopyrimidine compounds and observed rapid pan-life cycle parasite killing. Whole genome sequencing of parasite clones identified two mutations in the P. falciparum cytoplasmic isoleucyl tRNA synthetase (cIRS) associated with resistance to thienopyrimidines, and genetically modified parasites engineered with these mutations also showed resistance. Further analysis confirmed that cIRS inhibition by thienopyrimidine compounds is mediated by targeting a non-competitive allosteric binding site and functions differently than other known cIRS inhibitors. Together these findings highlight Plasmodium cIRS as a critical target for developing pan-life stage antimalarial compounds. —CF [ABSTRACT FROM AUTHOR]

New chiral ligands could be obtained by introducing proline moieties and imidazoline moieties to binaphthyl skeletons. The chiral ligands exhibited balanced rigidity and flexibility which could allow the change of the conformations during the reactions on one hand, and could provide sufficient asymmetric induction on the other. The proline moiety could act as a linker connecting the binaphthyl skeletons and the imidazoline moieties as well as a coordinating group for the central metal, and the electronic and steric properties of the imidazoline groups could be carefully fine-tuned by the use of different substituents. In the presence of Cu(II) catalyst bearing such chiral ligands, aza-Friedel-Crafts reaction of 1-naphthols and electron-rich phenols with isatin-derived ketimines provided the desired products with good to excellent yields and up to 99 % ee. The reactions showed good scalability, and excellent ee could still be obtained when the reaction was carried out in gram-scale., (© 2024 Wiley-VCH GmbH.)

The enantioselective Pictet‐Spenlger reaction of tryptamines and diketo compounds catalyzed by a polymer‐supported phosphoric acid (TRIP) has been accomplished for the first time in continuous flow. Using this approach, a diverse library of quaternary tryptolines has been synthesized in 36–95% yield with 39–99% enantiomeric excess. The scalability of the reaction has been demonstrated in continuous flow, with a residence time of only 24 minutes. The robust immobilized catalyst has been recycled and reused multiple times in batch and flow. The synthesis of the chiral precursors of Tadalafil, the Iboga‐type alkaloid (+)‐Tabertinggine and antimalarial spiroindolinones has been achieved in batch and continuous‐flow. [ABSTRACT FROM AUTHOR]

Duchenne Muscular Dystrophy (DMD), the most common form of muscular dystrophies, is characterized by progressive and generalized muscle weakness. The weakness of the trunk and other muscle groups leads these patients to perform motor compensation strategies to maintain their lower limb functionality for gait quality and for tasks such as getting up from a sitting position. In this cross-sectional observational study, we described and quantified trunk, gait, and sit-to-stand motor compensation strategie s in different stages of this disease. Thirty-one ambulatory 5–18-year-old children and adolescents with a diagnosis of DMD, underwent cognitive assessment with the Mental Mini-Examination (MMSE) and motor assessment with the Vignos scale, Segmental Assessment of Trunk Control (SATCo-BR), Timed Up and Go test (TUG Test), and 10-m walk test. We found strong correlations between trunk and gait compensations, and identified motor compensation strategies characteristic of certain DMD classifications. Also, these lower limb and trunk compensations related to disease staging (Vignos) such that compensations were fewer for patients at relatively better disease staging. [ABSTRACT FROM AUTHOR]

A potential three component reaction strategy has been devised to generate nature inspired β-carboline N-fused pyrroles containing pyridine tethers. These scaffolds were afforded in high yields via a one-pot cascade regioselective reaction of diverse Kumujian C, 2-aminopyridines and alkyne derivatives under Cu(II)-catalysis. A library of 32 novel indolizino[8,7-b]indole derivatives with pyridine tethers has been developed. The current protocol offers excellent regioselectivity, high atom-economy and significant structural diversity. [ABSTRACT FROM AUTHOR]

We report herein an asymmetric Pictet–Spengler reaction of α‐ketoesters. In the presence of a catalytic amount of simple alanine‐derived squaramide and p‐nitrobenzoic acid, reaction of tryptamines with methyl 2‐oxoalkanoates afforded the corresponding 1‐alkyl‐1‐methoxycarbonyl tetrahydro‐β‐carbolines (THBCs) in high yields and ee values. A primary kinetic isotope effect (KIE=4.5) using C2‐deteurium‐labelled tryptamine indicates that rearomatization through deprotonation of the pentahydro‐β‐carbolinium ion could be the rate‐ and enantioselectivity‐determining step. A concise enantioselective total synthesis of (+)‐alstratine A, a hexacyclic cagelike monoterpene indole alkaloid, featuring this reaction as a key step, was subsequently accomplished. Remeasurement of the [a]D value of the natural product indicates that natural alstratine A is dextrorotatory rather than levorotatory as it was initially reported in the isolation paper. [ABSTRACT FROM AUTHOR]

This review examines the presence and evolution of thyroid‐like systems in selected aquatic invertebrates to determine the potential use of these organisms in screens for vertebrate thyroid hormone axis disrupting chemicals (THADCs). Such a screen might support the phasing out of some vertebrate testing. Although arthropods including crustaceans do not contain a functional thyroid signaling system, elements of such a system exist in the aquatic phyla mollusks, echinoderms, tunicates, and cephalochordates. These phyla can synthesize thyroid hormone, which has been demonstrated in some groups to induce the nuclear thyroid hormone receptor (THR). Thyroid hormone may act in these phyla through interaction with a membrane integrin receptor. Thyroid hormone regulates inter alia metamorphosis but, unlike in vertebrates, this does not occur via receptor activation by the ligands triiodothyronine (T3) and thyroxine (T4). Instead, the unliganded nuclear receptor itself controls metamorphosis in mollusks, echinoderms, and tunicates, whereas the T3 derivative tri‐iodothyroacetic acid (TRIAC) acts as a THR ligand in cephalochordates. In view of this, it may be possible to develop an invertebrate‐based screen that is sensitive to vertebrate THADCs that interfere with thyroid hormone synthesis or metabolism along with interaction with membrane receptors. The review makes some recommendations for the need to develop an appropriate test method. Integr Environ Assess Manag 2023;19:63–82. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). KEY POINTS: This article examines thyroid‐like hormone systems in invertebrates and finds that they exist in several groups, including mollusks, echinoderms, tunicates, and cephalochordates.It is concluded that some invertebrate groups may provide a suitable basis for the development of screening tests for certain chemicals that disrupt the thyroid systems of vertebrates.It is likely that invertebrate‐based tests for vertebrate thyroid disrupters will be able to detect those that interfere with thyroid hormone synthesis and metabolism, but not those that act agonistically or antagonistically at the thyroid receptor.The development of invertebrate‐based tests for vertebrate thyroid disrupters would likely reduce the need for some vertebrate screening tests, which would be desirable from an ethical point of view. [ABSTRACT FROM AUTHOR]

We rely on vision more than on any other sense to obtain information about our environment. Hence, the loss or even impairment of vision profoundly affects our quality of life. Diet or food components have already demonstrated beneficial effects on the development of retinal diseases. Recently, there has been a growing interest in resources from marine animals and plants for the prevention of retinal diseases through nutrition. Especially fish intake and omega-3 fatty acids have already led to promising results, including associations with a reduced incidence of retinal diseases. However, the underlying molecular mechanisms are insufficiently explained. The aim of this review was to summarize the known mechanistic effects of marine resources on the pathophysiological processes in retinal diseases. We performed a systematic literature review following the PRISMA guidelines and identified 107 studies investigating marine resources in the context of retinal diseases. Of these, 46 studies described the underlying mechanisms including anti-inflammatory, antioxidant, antiangiogenic/vasoprotective, cytoprotective, metabolic, and retinal function effects, which we critically summarize. We further discuss perspectives on the use of marine resources for human nutrition to prevent retinal diseases with a particular focus on regulatory aspects, health claims, safety, and bioavailability. [ABSTRACT FROM AUTHOR]

Spiro[pyran‐4‐quinolines] were synthesized in two steps from exo‐glycals. The first step involved the double additions of aniline (or substituted anilines) to produce C,N‐glycosides. The next step was to eliminate the anomeric N‐aryl group by formation of benzophenone‐derived imine, followed by in situ intramolecular Friedel−Crafts alkylation. The resulting (1S)‐spiro[pyran‐4‐quinolines] were obtained in 60–72 % overall yields with exclusive (from the reactions of exo‐galactals) or high stereoselectivity (from those of exo‐glucals with m‐substituted anilines), respectively. Additionally, exo‐galactals were found suitable to perform the two steps consecutively in one‐pot at 75 °C. [ABSTRACT FROM AUTHOR]

A thiourea organocatalyst efficiently promoted the asymmetric cascade Michael/Michael reactions between isatin-derived trifluoromethylacrylate and α-alkylidene succinimide, resulting in high yields of spirooxindole derivatives. These compounds exhibit vicinal all-carbon quaternary stereocenters and bear a trifluoromethyl group, with excellent enantioselectivities reaching up to 99 % ee. This work represents the first successful organocatalyst application for the direct construction of vicinal all-carbon quaternary stereocenters, featuring a trifluoromethyl group., (© 2023 Wiley-VCH GmbH.)

Retinoic acid, the active metabolite of Vitamin A, is important for the appropriate development of the nervous system (e.g., neurite outgrowth) as well as for cognition (e.g., memory formation) in the adult brain. We have shown that many of the effects of retinoids are conserved in the CNS of the mollusc, Lymnaea stagnalis. RXRs are predominantly nuclear receptors, but the Lymnaea RXR (LymRXR) exhibits a non-nuclear distribution in the adult CNS, where it is also implicated in non-genomic retinoid functions. As such, we developed a CNS Drosophila organ culture-based system to examine the transcriptional activity and ligand-binding properties of LymRXR, in the context of a live invertebrate nervous system. The novel ligand sensor system was capable of reporting both the expression and transcriptional activity of the sensor. Our results indicate that the LymRXR ligand sensor mediated transcription following activation by both 9-cis RA (the high affinity ligand for vertebrate RXRs) as well as the vertebrate RXR synthetic agonist, SR11237. The LymRXR ligand sensor was also activated by all-trans RA, and to a much lesser extent by the vertebrate RAR synthetic agonist, EC23. This sensor also detected endogenous retinoid-like activity in the CNS of developing Drosophila larvae, primarily during the 3rd instar larval stage. These data indicate that the LymRXR sensor can be utilized not only for characterization of ligand activation for studies related to the Lymnaea CNS, but also for future studies of retinoids and their functions in Drosophila development. [ABSTRACT FROM AUTHOR]

Molecular iodine in combination with TBHP offers an advanced concept for organic synthesis and catalysis by improving the selectivity and sustainability of organic transformations. It leads to the development of metal free greener protocols under ambient conditions either as a catalytic duo or as a reagent system in combination with an additive. The advent of this indispensable tool led to formation of complex organic architectures empowering novel reaction pathways through C−H functionalization, cyclization, cycloaddition, rearrangement, sulfonylation/sulfenylation and oxidation reactions in organic synthesis. [ABSTRACT FROM AUTHOR]

The creation of structurally diverse chemical entities from fairly simple biorefinery products remains a challenge. In this work 5‐hydroxymethylfurfural (HMF) was identified as a key synthon for preparing highly complex cyclopentenones (CP) via tandem 1,4‐addition/elimination/remote lactone activation to external O‐ and N‐nucleophiles in δ‐lactone‐fused‐CPs hotspots. This scaffold was also reactive enough to be incorporated into model cysteine‐peptides in low concentrations, paving the way to a potential translation generating complexity in the synthesis of small peptides. The new enones also exhibited activity against intraerythrocytic Plasmodium falciparum (IC50=1.32 μm). [ABSTRACT FROM AUTHOR]

An easy atom‐economic methodology for the synthesis of tetrahydro‐β‐carbolino‐spiroindolone/ spiroacenapthylene scaffold in one step from tryptamine and isatin have been done via Pictet‐Spengler Reaction using lemon juice as a biocatalyst system. The reaction is clean and convenient for the synthesis of spiroindolones. The product was separated via easy chromatographic technique (column/flash) and characterized by 1D NMR (1H, 13 C and DEPT) and HRMS analysis. Bio evaluation against four cancer cell lines (MCF‐7, SH‐SY5Y, HepG2 and HEK 293) shows good positive indication of activity for 3 g, 3 h and 3 i. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Inonu University Health Services Vocational School / Inönü Üniversitesi Sağlık Hizmetleri Meslek Yüksekokulu Dergisi is the property of Inonu Universitesi Saglik Hizmetleri Meslek Yuksekokulu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A multistep and diversity-oriented synthetic route aiming at the A 3 coupling/domino cyclization of o-ethynyl anilines, aldehydes and s-amines is described. The preparation of the corresponding precursors included a series of transformations, such as haloperoxidation and Sonogashira cross-coupling reactions, amine protection, desilylation and amine reduction. Some products of the multicomponent reaction underwent further detosylation and Suzuki coupling. The resulting library of structurally diverse compounds was evaluated against blood and liver stage malaria parasites, which revealed a promising lead with sub-micromolar activity against intra-erythrocytic forms of Plasmodium falciparum. The results from this hit-to-lead optimization are hereby reported for the first time., (© 2023 Wiley-VCH GmbH.)

Organocatalytic Friedel‐Crafts aminoalkylation reaction is demonstrated in this study for the construction of biologically important hybrid molecular architectures of carbazole containing 3‐amino oxindoles using bifunctional cinchonidine derived thiourea organocatalyst. The Friedel‐Crafts functionalization of 4‐hydroxy carbazole with isatin derived ketimines well performed with a wide range of substrates resulted in excellent yields (up to 95 %) and enantioselectivities (up to 99 % ee) of the desired products. A minimal catalyst loading (0.5 mol%) was utilized at ambient temperatures under mild reaction conditions. [ABSTRACT FROM AUTHOR]

The biological and medicinal importance of oxindole-derived spirocycles is now well-established, and has inspired the development of numerous creative synthetic strategies. Here we report an efficient formal [3+2]-cycloaddition of isatin-derived N-trifluoroethyl ketimines with a series of benzylidinemalononitrile and benzylidineindandione dipolarophiles catalysed by a cinchona-derived thiourea catalyst. The reaction affords a series of functionalized spiro-pyrrolidinoxindole products with up to four contiguous stereocentres in excellent yields, ee and d.r. (up to 98% yield, 97% ee, and >100 : 1 d.r.). These products share a common core scaffold with compounds previously found to have anti-tumour, anti-microbial and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Synaptic pruning during adolescence is important for appropriate neurodevelopment and synaptic plasticity. Aberrant synaptic pruning may underlie a variety of brain disorders such as schizophrenia, autism and anxiety. Dopamine D2 receptor (Drd2) is associated with several neuropsychiatric diseases and is the target of some antipsychotic drugs. Here we generate self-reporting Drd2 heterozygous (SR-Drd2+/−) rats to simultaneously visualize Drd2-positive neurons and downregulate Drd2 expression. Time course studies on the developing anterior cingulate cortex (ACC) from control and SR-Drd2+/− rats reveal important roles of Drd2 in regulating synaptic pruning rather than synapse formation. Drd2 also regulates LTD, a form of synaptic plasticity which includes some similar cellular/biochemical processes as synaptic pruning. We further demonstrate that Drd2 regulates synaptic pruning via cell-autonomous mechanisms involving activation of mTOR signaling. Deficits of Drd2-mediated synaptic pruning in the ACC during adolescence lead to hyper-glutamatergic function and anxiety-like behaviors in adulthood. Taken together, our results demonstrate important roles of Drd2 in cortical synaptic pruning. Synaptic pruning is important during development and synaptic plasticity. Here, the authors show that the dopamine D2 receptor (Drd2) in the anterior cingulate cortex regulates synaptic pruning, affecting LTD and behaviour in transgenic rats. [ABSTRACT FROM AUTHOR]

Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold-catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin-derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Herein, we have disclosed pentafluorophenol as an operative catalyst for synthesizing (spirocyclic) tetrahydro-β-carbolines via the Pictet-Spengler reaction. This straightforward catalytic protocol works under mild conditions resulting indole alkaloids in excellent yield with remarkable functional group tolerance, including late-stage modifications. This transformation demonstrates a practical and adaptable approach to produce a highly effective gram-scale synthesis of the natural alkaloid Komavine and enables the synthesis of the commercial drug Tadalafil., (© 2023 Wiley-VCH GmbH.)