ConspectusDonor–acceptor (D–A) cyclopropanes have gained increased momentum over the past two decades. The use of these highly strained three-membered entities paved the way to innovative and origi...

Exploiting Heavier Organochalcogen Compounds in Donor-Acceptor Cyclopropane Chemistry.

(3 + 2)-Cycloaddition of Donor-Acceptor Cyclopropanes with Selenocyanate: Synthesis of Dihydroselenophenes and Selenophenes

We present (3+2)- and (4+2)-cycloadditions of donor-acceptor (D-A) cyclopropanes and cyclobutanes with N-sulfinylamines and a sulfur diimide, along with a one-pot, two-step strategy for the formal insertion of HNSO 2 into D-A cyclopropanes. These are rare examples of cycloadditions with D-A cyclopropanes and cyclobutanes whereby the 2π component consists of two different heteroatoms, thus leading to five- and six-membered rings containing adjacent heteroatoms.

Cycloadditions of Donor-Acceptor Cyclopropanes and -butanes using S=N-Containing Reagents: Access to Cyclic Sulfinamides, Sulfonamides, and Sulfinamidines

Structurally important benzobicyclo[3.3.1]nonane derivatives were synthesized by a gallium trichloride mediated reaction of readily available donor-acceptor cyclopropanes (DACs) with 1,3-dienes as a one-pot cascade ionic [2 + 4]-cycloaddition/Friedel-Crafts-type cyclization process. At the first stage, DACs act as sources of formal gallium 1,2-zwitterionic complexes to give 6-benzylcyclohex-3-ene-1,1-dicarboxylates that are converted under certain conditions in the presence of GaCl3 to give benzobicyclo[3.3.1]nonanes in 30-74% yields. The process is tolerant of varying substituents at different positions of the main framework. Further, potentially useful modifications of benzobicyclo[3.3.1]nonane derivatives are demonstrated. 2-Cyclopropylbutadiene reacts with DAC at higher temperature more deeply with cleavage of three-membered rings in both cyclopropane substrates, and twofold alkylation of the Ph-substituent at ortho- and meta-positions, that leads to a 1,2,7,8,9,10-hexahydro-6H-7,10a-methanocycloocta[cd]indene skeleton. Cyclopropane-1,1-diesters containing a bulky substituent in the ester group react with isoprene in a different way to give bicyclic lactones containing a 2-oxabicyclo[2.2.2]octan-3-one moiety.

GaCl3-Mediated Cascade [2 + 4]-Cycloaddition/[4 + 2]-Annulation of Donor-Acceptor Cyclopropanes with Conjugated Dienes: Strategy for the Construction of Benzobicyclo[3.3.1]nonane Skeleton.

Diet is an essential modulator of the microbiota - gut - brain communication in health and disease. Consequently, diet-induced microbiome states can impact brain health and behaviour. The integration of microbiome into clinical nutrition perspectives of brain health is sparse. This review will thus focus on emerging evidence of microbiome-targeted dietary approaches with the potential to improve brain disorders.Research in this field is evolving toward randomized controlled trials using dietary interventions with the potential to modulate pathways of the microbiota - gut - brain-axis. Although most studies included small cohorts, the beneficial effects of Mediterranean-like diets on symptoms of depression or fermented foods on the immune function of healthy individuals shed light on how this research line can grow. With a clinical nutrition lens, we highlight several methodological limitations and knowledge gaps, including the quality of dietary intake information, the design of dietary interventions, and missing behavioural outcomes.Findings in diet - microbiome - brain studies can have groundbreaking implications in clinical nutrition practice and research. Modulating brain processes through diet via the gut microbiota raises numerous possibilities. Novel dietary interventions targeting the microbiota - gut - brain-axis can offer various options to prevent and treat health problems such as mental disorders. Furthermore, knowledge in this field will improve current nutritional guidelines for disease prevention. 

Diet and the microbiota–gut–brain-axis: a primer for clinical nutrition

Ferrocenyl thioketones reacted with donor-acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields. In all studied cases, dimethyl 2-arylcyclopropane dicarboxylates reacted with the corresponding aryl ferrocenyl thioketones in a completely diastereoselective manner to form single products in which (C-2)-Ar and (C-5)-ferrocenyl groups were oriented in a cis-fashion. In contrast, the same cyclopropanes underwent reaction with alkyl ferrocenyl thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-16-109.pdf

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor-acceptor cyclopropanes.

Background Gut microbiota-based therapeutic strategies, such as probiotic and prebiotic preparations, may benefit mental health. However, commonly consumed fermented and prebiotic-containing foods have not been well-tested. The aim of the present study was to determine whether consumption of fermented food and food-derived prebiotics is associated with cognitive performance, depressive, and anxiety symptoms in psychiatrically healthy medical students under psychological stress. Methods The study protocol with data analysis plan was prospectively registered. Food consumption was evaluated with a 7-day dietary record. Cognitive performance was modeled with academic examination performance in relation to subject knowledge. Pre-exam depressive and anxiety symptoms were assessed with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Results In total, 372 medical students (22.7 ± 1.1 years of age, 66% female) completed the study. No relationship was observed between cognitive performance under stress and either fermented food (adjusted β 0.02, 95% CI −0.07–0.11, p = 0.63) or food-derived prebiotics consumption (adjusted β −0.00, 95% CI −0.09–0.09, p = 0.99). High intake of fermented food was associated with more severe depressive (adjusted β 0.11, 95% CI 0.01–0.20, p = 0.032) and anxiety symptoms under stress (adjusted β 0.13, 95% CI 0.04–0.22, p = 0.0065); however, no such link was observed for food-derived prebiotics (adjusted β 0.03, 95% CI −0.07–0.13, p = 0.50 and −0.01, 95% CI −0.11–0.08, p = 0.83, for depression and anxiety, respectively). Conclusions Under psychological stress in medical students, consumption of fermented food and food-derived prebiotics appears to be not associated with cognitive performance. High intake of fermented food, but not food-derived prebiotics, may be associated with severity of depressive and anxiety symptoms. The safety of fermented food in this regard therefore requires further clarification.

https://www.frontiersin.org/articles/10.3389/fnut.2022.850249/pdf

Association Between Consumption of Fermented Food and Food-Derived Prebiotics With Cognitive Performance, Depressive, and Anxiety Symptoms in Psychiatrically Healthy Medical Students Under Psychological Stress: A Prospective Cohort Study

Condensation of diacetyl monooxime with formaldimines derived from alkoxyamines in glacial acetic acid at room temperature leads to corresponding 2-unsubstituted imidazole N-oxides bearing an alkoxy substituent at the N(1) atom of the imidazole ring. Subsequent O-benzylation afforded, depending on the type of alkylating agent, either symmetric or nonsymmetric alkoxyimidazolium salts considered as structural analogues of naturally occurring imidazole alkaloids, lepidilines A and C. Some of the obtained salts were tested as precursors of nucleophilic heterocyclic carbenes (NHCs), which in situ reacted with elemental sulfur to give the corresponding N-alkoxyimidazole-2-thiones. The cytotoxic activity of selected 4,5-dimethylimidazolium salts bearing either two benzyloxy or benzyloxy and 1-adamantyloxy groups at N(1) and N(3) atoms was evaluated against HL-60 and MCF-7 cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Notably, in two cases of alkoxyimidazolium salts, no effect of the counterion exchange (Br− → PF6−) on the biological activity was observed.

Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C

Lewis-Acid-Catalyzed (3+2)-Cycloadditions of Donor-Acceptor Cyclopropanes with Thioketenes

Starting with fluorinated benzylamines, a series of 2-unsubstituted imidazole N-oxides was prepared and subsequently deoxygenated in order to prepare the corresponding imidazoles. The latter were treated with benzyl halides yielding imidazolium salts, which are considered fluorinated analogues of naturally occurring imidazolium alkaloids known as lepidilines A and C. A second series of oxa-lepidiline analogues was obtained by O-benzylation of the initially synthetized imidazole N-oxides. Both series of imidazolium salts were tested as anticancer and antiviral agents. The obtained results demonstrated that the introduction of a fluorine atom, fluoroalkyl or fluoroalkoxy substituents (F, CF3 or OCF3) amplifies cytotoxic properties, whereas the cytotoxicity of some fluorinated lepidilines is promising in the context of drug discovery. All studied compounds revealed a lack of antiviral activity against the investigated viruses in the nontoxic concentrations.

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Mateusz Kowalczyk

Papers

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor-acceptor cyclopropanes.

Association Between Consumption of Fermented Food and Food-Derived Prebiotics With Cognitive Performance, Depressive, and Anxiety Symptoms in Psychiatrically Healthy Medical Students Under Psychological Stress: A Prospective Cohort Study

Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C

Lewis-Acid-Catalyzed (3+2)-Cycloadditions of Donor-Acceptor Cyclopropanes with Thioketenes

Fluorinated Analogues of Lepidilines A and C: Synthesis and Screening of Their Anticancer and Antiviral Activity