Visible light-triggered selective C(sp2)-H/C(sp3)-H coupling of benzenes with aliphatic hydrocarbons.

The direct and selective coupling of benzenes with aliphatic hydrocarbons is a promising strategy for C(sp2)-C(sp3) bond formation using readily available starting materials, yet it remains a significant challenge. In this study, we have developed a simplified photochemical system that incorporates catalytic amounts of iron(III) halides as multifunctional reagents and air as a green oxidant to address this synthetic problem. Under mild conditions, the reaction between a strong C(sp2)-H bond and a robust C(sp3)-H bond has been achieved, affording a broad range of cross-coupling products with high yields and commendable chemo-, site-selectivity. The iron halide acts as a multifunctional reagent that responds to visible light, initiates C-centered radicals, induces single-electron oxidation to carbocations, and participates in a subsequent Friedel-Crafts-type process. The gradual release of radical species and carbocation intermediates appears to be critical for achieving desirable reactivity and selectivity. This eco-friendly, cost-efficient approach offers access to various building blocks from abundant hydrocarbon feedstocks, and demonstrates the potential of iron halides in sustainable synthesis.

Photochemical Synthesis of S,N,O-Containing Polyheterocycles via an α-C(sp3)-H Functionalization/Radical Cyclization Cascade.

A highly effective approach based on an organophotocatalytic α-C(sp3)-H functionalization/radical cyclization cascade has been developed. This method enables the synthesis of various tricyclic heterocycles containing S, O, and N atoms with excellent site selectivity and diastereoselectivity. Mechanistic investigations have confirmed that the reaction involves photoredox-triggered C(sp3)-H cleavage followed by a radical cyclization and aromatization process. These findings are expected to pave the way for developing cost-effective tandem radical reactions and synthesizing heterocyclic drugs.

Fe-Catalyzed Aliphatic C-H Methylation of Glycine Derivatives and Peptides.

Direct and selective C-H methylation is a powerful tool with which to install methyl groups into organic molecules, and is particularly useful in pharmaceutical chemistry. However, practical methods for such modification of biologically interesting targets have been rarely developed. We here report an iron-catalyzed C(sp3 )-H methylation reaction of glycine derivatives, peptides and drug-like molecules in an alcohol in the presence of di-tert-butyl peroxide. A readily available iron catalyst plays multiple roles in the transformation, which accelerates oxidation of C-N bonds to C=N double bonds, activates imine intermediates as Lewis acids by bidentate chelation, and at the same time facilitates cleavage of the peroxide to generate methyl radicals. A variety of methylated N-aryl glycine derivatives and peptides were obtained in good yield and with excellent chemo- and site-selectivity. This reaction is scalable, easily managed, and can be completed within 1-2 h. It features an economic, bio-friendly catalyst, a green solvent and low toxic reagents, and will provide effective access to precise C-H modification of biomolecules and natural products.

Association between PPAR-γ2 gene polymorphisms and diabetic retinopathy risk: a meta-analysis.

A close association between peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) and the development of diabetic retinopathy (DR) has been previously suggested. Herein, a meta-analysis was conducted to explore the association between PPAR-γ2 polymorphisms and DR risk by performing a systematic search and quantitative analysis. Overall, fourteen articles involving 10,527 subjects were included. The pooled results did not reveal an association between PPAR-γ2 rs1801282 C/G and DR susceptibility in the overall population (e.g., the dominant model: CG+GG vs. CC, OR=0.85, 95% CI=0.69-1.06, P=0.15, I2=62.9%). Furthermore, heterogeneity tests, cumulative analyses, sensitivity analyses, and publication bias analyses were conducted and showed that the results were robust. Similarly, race-based subgroup analyses and other subgroup analyses did not reveal an association between the rs1801282 C/G and DR susceptibility. In addition, no significant association was observed between PPAR-γ2 rs3856806 C/T polymorphism and DR risk (e.g., the dominant model: CT+TT vs. CC, OR=1.12, 95%CI=0.91-1.37, P=0.28, I2=27.0%). Overall, based on the current sample size and the level of evidence presented in the study, the results suggest that PPAR-γ2 gene polymorphisms are not associated with DR risk.

Electrochemical Synthesis of 1-Naphthols by Intermolecular Annulation of Alkynes with 1,3-Dicarbonyl Compounds.

C-centered radical cyclization under electrochemical conditions is a feasible strategy for constructing cyclic structures. Reported herein is the electrochemical synthesis of highly functionalized 1-naphthols using alkynes and 1,3-dicarbonyl compounds by (4 + 2) annulation of C-centered radical. Electrolysis was conducted with Cp2Fe as redox catalyst, thereby eliminating the use of oxidants and transition-metal catalysts. The synthesized 1-naphthol compounds showed good antitumor activity in vitro, and further studies indicated that compound 3bl induced tumor cell apoptosis.

Association between CD14 rs2569190 C>T polymorphism and ischemic stroke susceptibility: a meta-analysis based on 5,277 subjects.

INTRODUCTION: Previous epidemiological studies have suggested that CD14 rs2569190 C>T polymorphism plays an important role in ischemic stroke (IS) risk, but the results were inconsistent. Therefore, we conducted a meta-analysis to determine the association between CD14 rs2569190 C>T polymorphism and IS susceptibility. METHODS: Online databases were searched from inception up to July 1, 2018, for studies concerning CD14 rs2569190 C>T polymorphism and its association with IS susceptibility. ORs and corresponding 95% CIs were calculated in the genetic models of each polymorphism locus with Stata Version 14.0. Furthermore, heterogeneity, meta-regression, accumulative analyses, sensitivity analyses, and publication bias were examined. RESULTS: Overall, 10 observed studies involving 5,277 subjects were included in this meta-analysis on CD14 rs2569190 C>T polymorphism. Generally, no significant associations were found between CD14 rs2569190 C>T polymorphism and IS risk (allele contrast of T vs C: OR =1.03, 95% CI =0.96-1.12, P=0.41, I2=27.8%; co-dominant models of CT vs CC: OR =1.01, 95% CI =0.81-1.25, P=0.95, I2=51.9%; co-dominant models of TT vs CC: OR =1.04, 95% CI =0.89-1.22, P=0.62, I2=25.1%; dominant model of CT + TT vs CC: OR =1.02, 95% CI =0.84-1.25, P=0.82, I2=51.4%; recessive model of TT vs CC + CT: OR =1.07, 95% CI =0.95-1.22, P=0.28, I2=0%), similar to the results in the subgroup analysis. CONCLUSION: The current evidence indicated that CD14 rs2569190 C>T polymorphism was not a critical risk factor for IS development.

Dietary conjugated linoleic acid modulates morphology, selective immune parameters, and gene expressions in the intestine of grass carp.

Conjugated linoleic acid (CLA) has been shown to exhibit anti-inflammatory properties in the intestine in mammals. However, the effect of CLA on intestinal immune response in fish is still unknown. Therefore, a 65-day growth trial was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) on morphology, selective immune parameters, and gene expressions in the intestine of grass carp. Seven isonitrogenous and isolipidic diets were formulated as follows: 0 (control), 0.5 (CLA0.5), 1 (CLA1), 1.5 (CLA1.5), 2 (CLA2), 2.5 (CLA2.5), and 3 (CLA3) g CLA per 100g of feed. RESULTS: showed that dietary supplementation of 1.5-3% CLA significantly (P < 0.05) increased the fold and enterocyte heights in the PI and MI of grass carp. Complement 3 (C3) and immunoglobulin M (IgM) contents in three intestinal segments were significantly (P < 0.05) higher in fish fed with CLA1.5 to CLA2.5 diets compared to fish fed the control diet. CLA1.5 to CLA2.5 diets significantly (P < 0.05) increased the mRNA expression levels of anti-inflammatory cytokines (IL-10 and TGFß1) and significantly (P < 0.05) reduced the mRNA expression levels of pro-inflammatory cytokines (IL-1ß, IL-8, and TNF-α) in the PI, MI, and DI. This improved expression of anti-inflammatory cytokines and the inhibited expression of pro-inflammatory cytokines in the intestine of grass carp, might be mediated via TLR4/NF-κB-signaling pathway. Our results suggested that CLA1.5 to CLA2 diets improved intestinal morphology, increased the expression of anti-inflammatory cytokines, and inhibited the expression of pro-inflammatory cytokines in the intestine of grass carp. In conclusion, dietary supplementation of 1.5%-2% CLA show the anti-inflammatory therapeutic potential in the intestine of grass carp. The anti-inflammatory therapeutic potential of CLA might be mediated via TLR4/NF-κB-signaling pathway.

Stabilization of peptides against proteolysis through disulfide-bridged conjugation with synthetic aromatics.

Peptides have been promising molecular scaffolds for the development of potential therapeutics with high affinity and specificity to biomacromolecules. However, their inherent proteolytic instability significantly hampers their biological applications. Strategies that can stabilize peptides against proteolytic digestion on the basis of noncovalent interactions-without extensive manipulation of the sequence or use of unnatural residues-are greatly desired. In this work, we developed a general, convenient, and efficient strategy for the stabilization of peptides against proteolysis, which involves noncovalent π-π interactions between aromatic amino acid residues in peptides and synthetic electron-deficient aromatics (NDI), together with the implication of steric hindrance (from the bulky NDI moiety), and the enhancement of peptide α-helicity. This strategy is complementary in concept to the conventional well-established covalent approaches for peptide stabilization, and is thus promising for being utilized, in combination with the latter ones, to circumvent the problem of proteolytic instability of peptides. We envisioned that this study should provide invaluable guidelines to the design and synthesis of organic molecule-peptide hybrids with significantly improved proteolytic resistance, and benefit the development of peptide therapeutics and probes.