Photocatalyzed Intramolecular [2+2] Cycloaddition of N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides.

N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides are converted into natural product inspired scaffolds via iridium photocatalyzed intramolecular [2+2] photocycloaddition. The protocol has a broad substrate scope, whilst operating under mild reaction conditions. Tethering four components forming a trisubstituted cyclobutane core builds rapidly high molecular complexity. Our approach allows the design and synthesis of a variety of tetrahydrocyclobuta[c]quinolin-3(1H)-ones, in yields ranging between 20-99 %, and with excellent regio- and diastereoselectivity. Moreover, it was demonstrated that the intramolecular [2+2]-cycloaddition of 1,7-enynes-after fragmentation of the cyclobutane ring-leads to enyne-metathesis-like products.

Recent Advances on Photoinduced Cascade Strategies for the Synthesis of N-Heterocycles.

Over the last decade, visible-light photocatalysis has proved to be a powerful tool for the construction of N-heterocyclic frameworks, important constituents of natural products, insecticides, pharmacologically relevant therapeutic agents and catalysts. This account highlights recent developments and established methods towards the photocatalytic cascades for preparation of different classes of N-heterocycles, giving emphasis on our contribution to the field.

Minisci C-H Alkylation of Heteroarenes Enabled by Dual Photoredox/Bromide Catalysis in Micellar Solutions*.

Aromatic heterocycles are omnipresent structural motifs in various natural products, pharmaceuticals and agrochemicals. This work describes a photocatalytic Minisci-type C-H functionalization of heteroarenes with non-activated alkyl bromides. The reaction avoids stoichiometric radical-promoters, oxidants, or acids, and is conducted using blue LEDs as the light source. The reactive carbon-centered alkyl radicals are generated by merging the photoredox approach with bromide anion co-catalysis and spatial pre-aggregation of reacting species in the micellar aqueous solutions. The obtained data highlight the critical importance of microstructuring and organization of the components in the reaction mixture.

Green Approach for Visible-Light-Induced Direct Functionalization of 2-Methylquinolines.

A transition metal- and oxidant-free visible light-photoinduced protocol for direct functionalization of 2-methylquinolines has been developed. This protocol enabled the C-H functionalization of substituted 2-methylquinolines with diacetyl or ethyl pyruvate, under environmentally friendly conditions. A mechanistic investigation based on density functional theory (DFT) calculations provided details about the origins of reactivity and selectivity.

Accuracy and Psychometric Properties of the Brazilian Version of the Montreal Cognitive Assessment as a Brief Screening Tool for Mild Cognitive Impairment and Alzheimer's Disease in the Initial Stages in the Elderly.

OBJECTIVE: To evaluate the applicability and the psychometric properties of Montreal Cognitive Assessment Brazilian Version (MoCA-BR) in the elderly, as well as comparing its accuracy as a tracking test for mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) with the accuracy of Mini-Mental State Examination (MMSE). METHOD: A transversal study was performed in 4 reference medical centers that care for the elderly. In all, 229 elderly participated in the study. To select the sample, the clinical history of the elderly, Pfeffer Functional Activities Questionnaire, and neuropsychological battery, apart from MMSE and MoCA-BR cognitive tests, were selected. The elderly were classified into control, MCI, and mild AD groups. RESULTS: There was a significant statistical difference between the MoCA-BR scores of the elderly and the control group, MCI, and mild AD (p < 0.001). The Cronbach alpha for MoCA-BR was 0.77, indicating a good internal consistency. The test-retest reliability was elevated, with intraclass correlation coefficient (ICC) 0.91. The inter-examiner reliability was excellent (ICC 0.96). The area under curve of the receiver operating characteristics curve was 0.95, when evaluating the ability of MoCA-BR to discriminate between the elderly with cognitive impairment and cognitively healthy elderly. CONCLUSIONS: The results of the study show that the Brazilian version of MoCA is a reliable cognitive tracking tool and is accurate for the detection of MCI and early stage AD, with good applicability on the elderly with education equal to or more than 4 years and adequate to discriminate between cognitively healthy elderly, and those with MCI and mild, proving to be superior to MMSE in tracking MCI and similar to this test when tracking mild AD.

Synthesis of Highly Substituted 1,2-Diazetidin-3-ones, Small-Ring Scaffolds for Drug Discovery.

1,2-Diazetidin-3-ones are readily accessible, small ring scaffolds that upon functionalization have the potential to produce diverse 3-dimensional structures for drug discovery. Thus, treatment of diazo hydrazides, obtained from simple hydrazides and malonyl half ester derivatives, followed by diazo transfer, with catalytic amounts of rhodium(II) acetate dimer results in intramolecular carbenoid N-H insertion to give 1,2-diazetidin-3-ones. Although subsequent functionalization reactions could be hampered by the lability of the 4-membered ring, a wide range of new derivatives was available by deprotection at N-1, and subsequent amide or urea formation. The structures of four four-membered rings was confirmed by X-ray crystallography; the compounds showed modest growth inhibitory activity in mammary carcinoma cells.

Diastereoselective Synthesis of Biologically Active Cyclopenta[b]indoles.

The cyclopenta[b]indole motif is present in several natural and synthetic biologically active compounds, being directly responsible for the biological effects some of them present. We described herein a three step sequence for the synthesis of cyclopenta[b]indoles with a great structural diversity. The method is based on an oxidative Michael addition of suitable indoles on the double bond of Morita-Baylis-Hillman adducts mediated by a hypervalent iodine reagent (IBX) to form ß-ketoesters, which were chemoselectively reduced with NaBH4 in THF to give the corresponding ß-hydroxy-esters. The diastereoisomeric mixture was then treated with a catalytic amount of triflic acid (20 mol %) to give cyclopenta[b]indoles with overall yields ranging from 8 to 73% (for 2 steps). The acid-catalyzed cyclization step gave the required heterocycles, via an intramolecular Friedel-Crafts reaction, with high diastereoselectivity, where only the trans product was observed. A mechanistic study monitored by ESI-(+)-MS was also conducted to collect evidence about the mechanism of this reaction. The new molecules herein synthesized were also evaluated against a panel of human cancer cells demonstrating a promising antitumoral profile.

Photoredox Catalysis toward 2-Sulfenylindole Synthesis through a Radical Cascade Process.

A radical cascade process initiated through visible-light induced thiyl radical coupling with ortho-substituted arylisocianides followed by an intramolecular cyclization and subsequent aromatization to access 2-sulfenylindoles is described. The key thiyl radicals are promptly generated via a hydrogen atom transfer event. The redox-neutral protocol features broad substrate scope, excellent functional group tolerance, and mild reaction conditions. Furthermore, the implementation of a continuous flow variant allows smooth scalability with a short residence time through process intensification.

Optimal Cutoff Scores for Dementia and Mild Cognitive Impairment in the Brazilian Version of the Montreal Cognitive Assessment among the Elderly.

OBJECTIVE: To propose cutoff scores for the Brazilian version of the Montreal Cognitive Assessment (MoCA-BR) stratified by education in order to detect mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) in the elderly. METHOD: A transversal study in health centers was performed on 159 elderly people with 4-12 years of education and 70 of their peers with over 12 years of schooling. The MoCA-BR cutoff scores for screening cognitive impairment were determined based on an ROC curve analysis. RESULTS: The ROC curve analysis indicated that cutoff scores under 20 were good for screening elderly people with cognitive impairment with more than 12 years of education, and scores under 21 were good for screening those with 4-12 years of education. CONCLUSIONS: MoCA-BR scores under 21 points (after adding 1 point to the elderly with ≤12 years of education) indicate a need to continue the diagnostic investigation with regular follow-ups.

Intramolecular radical cyclization approach to access highly substituted indolines and 2,3-dihydrobenzofurans under visible-light.

The combination of visible-light and tris(trimethylsilyl)silane promoting intramolecular reductive cyclization protocol for the synthesis of functionalized indolines and 2,3-dihydrobenzofurans has been developed. The transformations occur in the absence of transition metal and additional photocatalyst. In addition, quantum yield (Φ) was determined and electron paramagnetic resonance spectroscopy was performed to better understand the reaction pathway.

Crystal structure of 3-(3,4,5-tri-meth-oxy-phen-yl)-1,2,3,4-tetra-hydro-cyclo-penta[b]indole-2-carb-oxy-lic acid.

In the title compound, C21H21NO5, obtained from a Morita-Baylis-Hillman adduct, the hydrogenated five-membered ring adopts a shallow envelope conformation, with the C atom bearing the carb-oxy-lic acid substituent deviating by 0.237 (1) Šfrom the mean plane of the other four atoms (r.m.s. deviation = 0.007 Å). The dihedral angle between the fused ring system (all atoms; r.m.s. deviation = 0.057 Å) and the pendant trimeth-oxy benzene ring is 66.65 (3)°. The C atoms of the meta-meth-oxy groups lie close to the plane of the benzene ring [deviations = 0.052 (1) and -0.083 (1) Å], whereas the C atom of the para-meth-oxy group is significantly displaced [deviation = -1.289 (1) Å]. In the crystal, carb-oxy-lic acid inversion dimers generate R 2 (2)(8) loops. The dimers are connected by N-H⋯O hydrogen bonds, forming [011] chains. A C-H⋯O inter-action is also observed.