Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions.

The enantioconvergent C(sp3)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N-alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp3)-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex. Thus, this kind of ligand could not only enhance the reducing capability of a copper catalyst to provide an enantioconvergent radical pathway but also avoid the coordination with other coordinating heteroatoms, thereby overcoming catalyst poisoning and/or chiral ligand displacement. This protocol covers a wide range of coupling partners (89 examples for activated racemic secondary/tertiary alkyl bromides/chlorides and (hetero)aromatic amines) with high functional group compatibility. When allied with follow-up transformations, it provides a highly flexible platform to access synthetically useful enantioenriched amine building blocks.

Cu(I)-Catalyzed Chemo- and Enantioselective Desymmetrizing C-O Bond Coupling of Acyl Radicals.

Transition-metal-catalyzed enantioselective functionalization of acyl radicals has so far not been realized, probably due to their relatively high reactivity, which renders the chemo- and stereocontrol challenging. Herein, we describe Cu(I)-catalyzed enantioselective desymmetrizing C-O bond coupling of acyl radicals. This reaction is compatible with (hetero)aryl and alkyl aldehydes and, more importantly, displays a very broad scope of challenging alcohol substrates, such as 2,2-disubstituted 1,3-diols, 2-substituted-2-chloro-1,3-diols, 2-substituted 1,2,3-triols, 2-substituted serinols, and meso primary 1,4-diols, providing enantioenriched esters characterized by challenging acyclic tetrasubstituted carbon stereocenters. Partnered by one- or two-step follow-up transformations, this reaction provides a convenient and practical strategy for the rapid preparation of chiral C3 building blocks from readily available alcohols, particularly the industrially relevant glycerol. Mechanistic studies supported the proposed C-O bond coupling of acyl radicals.

Cu-catalysed enantioselective radical heteroatomic S-O cross-coupling.

The transition-metal-catalysed cross-coupling reaction has established itself as one of the most reliable and practical synthetic tools for the efficient construction of carbon-carbon/heteroatom (p-block elements other than carbon) bonds in both racemic and enantioselective manners. In contrast, development of the corresponding heteroatom-heteroatom cross-couplings has so far remained elusive, probably due to the under-investigated and often challenging heteroatom-heteroatom reductive elimination. Here we demonstrate the use of single-electron reductive elimination as a strategy for developing enantioselective S-O coupling under Cu catalysis, based on both experimental and theoretical results. The reaction manifests its synthetic potential by the ready preparation of challenging chiral alcohols featuring congested stereocentres, the expedient valorization of the biomass-derived feedstock glycerol, and the remarkable catalytic 4,6-desymmetrization of inositol. These results demonstrate the potential of enantioselective radical heteroatomic cross-coupling as a general chiral heteroatom-heteroatom formation strategy.

Copper-Catalyzed anti-Selective Radical 1,2-Alkylarylation of Terminal Alkynes.

A copper-catalyzed highly anti-selective radical 1,2-alkylarylation of terminal alkynes with aryl boronic acids and alkyl bromides has been established. The reaction exhibits high compatibility with a wide range of terminal alkynes and diverse aryl boronic acids, thus providing facile access to various stereodefined trisubstituted alkenes in high yield under mild reaction conditions. Preliminary mechanistic investigations support the formation of alkyl radicals and their subsequent addition to alkynes in the reaction.

Quality improvement effects of electrolyzed water on rice noodles prepared with semidry-milled rice flours.

To investigate the effects of electrolyzed water treatment on the qualities of rice noodles prepared with semidry- milled rice flour, pasting properties and thermal properties of rice flour, and the cooking and textural properties of rice noodles were determined. Higher peak viscosity and lower melting enthalpy were observed in electrolyzed water (EW) treated rice flour. The hardness, gumminess and chewiness of rice noodle in slightly acidic electrolyzed water treated rice noodles with available chlorine concentration (ACC) 20.32 mg/L were increased significantly (p < 0.05). The cooking loss decreased significantly in strong acidic electrolyzed water treated noodles with ACC 10.09 mg/L treatment (p < 0.05). The results indicated that EW could promote the gelatinization of rice flour, and improve the textural qualities of rice noodles. Therefore EW was appropriate to be used in rice noodle production.

Desymmetrization of unactivated bis-alkenes via chiral Brønsted acid-catalysed hydroamination.

Although great success has been achieved in catalytic asymmetric hydroamination of unactivated alkenes using transition metal catalysis and organocatalysis, the development of catalytic desymmetrising hydroamination of such alkenes remains a tough challenge in terms of attaining a high level of stereocontrol over both remote sites and reaction centers at the same time. To address this problem, here we report a highly efficient and practical desymmetrising hydroamination of unactivated alkenes catalysed by chiral Brønsted acids with both high diastereoselectivity and enantioselectivity. This method features a remarkably broad alkene scope, ranging from mono-substituted and gem-/1,2-disubstituted to the challenging tri- and tetra-substituted alkenes, to provide access to a variety of diversely functionalized chiral pyrrolidines bearing two congested tertiary or quaternary stereocenters with excellent efficiency under mild and user-friendly synthetic conditions. The key to success is indirect activation of unactivated alkenes by chiral Brønsted acids via a concerted hydroamination mechanism.

Recent Advances in First-Row Transition Metal/Chiral Phosphoric Acid Combined Catalysis.

Since the pioneering independent reports of Akiyama and Terada, the use of chiral phosphoric acids (CPAs) and derivatives as a versatile tool for asymmetric synthesis with good reactivity, regioselectivity, diastereoselectivity and enantioselectivity has emerged, forming an important part of the implementation of asymmetric counteranion-directed catalysis reported to date. In these achievements, the combination of metals with CPAs has enabled various catalytic modes beyond the scope of typical acid catalysis, such as relay catalysis, ion-pairing catalysis, and binary acid catalysis. The first-row transition metals (Sc-Zn) are considered to be sustainable transition metals and have received a great deal of attention. These naturally abundant metals display excellent Lewis acidity and function as powerful redox catalysts in synthesis involving both one and two-electron transfers. Hence, in this chapter, we summarize recent advances in the development of asymmetric reactions using a combination of first-row transition metals and CPAs. Furthermore, we provide a detailed discussion of the mechanisms involved in order to understand the interaction of the metal/phosphate and the origins of the asymmetric control of the transformations.

Effect of electrolyzed water on enzyme activities of triticale malt during germination.

Triticale malt can be used as a source of enzymes or as a raw material for the production of functional foods. In this study, triticale malt was produced by soaking triticale seeds either in tap water (TW) or slightly acidic electrolyzed water (SAEW) and then rinsing with TW, SAEW, or alkaline electrolyzed water (AEW). We determined the length of the hypocotyl of triticale malt and the activities of α-amylase, phytase, proteases, and lipase during 4 days of germination. The electrolyzed water (EW) treatments promoted the growth of triticale malt. On the 4th day of germination, the hypocotyl length of triticale malt soaked in TW and watered with SAEW was 24.57% longer than that of triticale malt soaked and watered with TW. The α-amylase, phytase, acidic protease, and lipase activities of triticale malt soaked in SAEW and watered with AEW were high on the 4th germination day (0.11, 1.24 × 10-4, 0.62, and 0.51 units/mg protein, respectively). The main finding of this study is that the use of EW, especially during the soaking procedure, may be a promising way to obtain triticale malt with high enzyme activity for use in the production of functional foods.

Achiral Pyridine Ligand-Enabled Enantioselective Radical Oxytrifluoromethylation of Alkenes with Alcohols.

A conceptually novel strategy with achiral pyridine as the ancillary ligand to stabilize high-valent copper species for the first asymmetric radical oxytrifluoromethylation of alkenes with alcohols under CuI /phosphoric acid dual-catalysis has been developed. The transformation features mild reaction conditions, a remarkably broad substrate scope and excellent functional group tolerance, offering an efficient approach to a wide range of trifluoromethyl-substituted tetrahydrofurans bearing an α-tertiary stereocenter with excellent enantioselectivity. Mechanistic studies support the presumed role of the achiral pyridine as a coordinative ligand on copper metal to stabilize the key transient reaction species involved in the asymmetric induction process.

Application of electrolyzed water on reducing the microbial populations on commercial mung bean sprouts.

The efficacy of acidic electrolyzed water (AEW) for reducing total bacteria, coliforms, yeast and mold counts on commercial mung bean sprouts was investigated. The impact of pH, available chlorine concentration (ACC) and the cleaning method on antimicrobial efficacy of AEW was studied. AEW with a pH of 4.47 reduced the total bacterial, coliform, and yeast and mold counts on mung bean sprouts by 1.23, 1.42 and 1.25 log CFU/g, respectively. The efficacy of AEW increased with increasing ACC, and further studies showed that its antimicrobial ability was based on a combination of pH and ACC values. Cleaning using ultrasonic waves enhanced the antimicrobial activity of electrolyzed water, achieving reduction of 2.46, 2.13 and 2.92 log CFU/g for total bacterial, yeast and mold, and coliform counts, respectively. These results have indicated that using ultrasonic waves as a cleaning method, combined with AEW, could be a promising way to reduce the microbial populations on mung bean sprouts.

Expression and functional characterization of PGRP6 splice variants in grass carp Ctenopharyngodon idella.

Peptidoglycan recognition proteins (PGRPs), which are evolutionarily conserved pattern recognition receptors from insects to mammals, recognize bacterial PGN and function in antibacterial innate immunity. The existence of alternative splicing is a common feature for PGRP family. Here the splicing pattern from the splicing at the 5' end of PGRP6 gene was identified in a teleost fish, the grass carp (Ctenopharyngodon idella). Four splice variants of grass carp PGRP6 were designated as gcPGRP6a, gcPGRP6b, gcPGRP6c and gcPGRP6d, respectively. Real-time PCR revealed the different expression of these variants in fish individuals and CIK cell line in response to stimulation with different microbial ligands. Immunofluorescence microscopy and Western blotting showed that the splice variants are intracellular protein. Cell lysates from Epithelioma papulosum cyprini (EPC) cells transfected with gcPGRP6 splice variants are able to bind microbial PAMPs including Lys-type PGN from Staphylococcus aureus, DAP-type PGN from Bacillus subtilis, glucan, mannan, and microorganisms including Streptococcus dysgalactiae, Flavobacterium columnare and Saccharomyces cerevisiae. Moreover, overexpression of gcPGRP6 variants inhibited earlier stage growth of intracellular bacteria. The data also identified a specific role for gcPGRP6c variant in the positive regulation of cytolytic molecule perforin, and for gcPGRP6a, gcPGRP6b and gcPGRP6c variants in positive regulation of antimicrobial peptides (AMPs). However, the gcPGRP6d variant, which encoded basically only the PGRP domain, failed to induce the expression of perforin and AMPs. It is suggested that fish PGRP6 splice variants have common and variant-specific function in innate immune response.

Expression and protective role of two novel NACHT-containing proteins in pathogen infection.

Lower vertebrates have been found to possess over 200 NACHT-domain encoding genes; but, to date, very little is known about their functional activity. This article describes the sequences and expression analysis of two zebrafish NACHT-containing proteins, namely NALPL1 and NALPL2. In addition, the functions of zebrafish NALPL1 and NALPL2, which are absent for both amino-terminal effector-binding domain (EBD) and carboxy-terminal ligand-recognition domain (LRD), were investigated for the first time in fish species. The predicted NALPL1 and NALPL2 proteins consist of 651 and 847 amino acids (aa), respectively, with both molecules only containing NACHT domain, which were different from other NACHT-family members. Phylogenetic analysis showed that zebrafish NALPL1 and NALPL2 have a closer relationship with mammalian NALP subfamily than NOD subfamily. The differential expression patterns of NALPL1 and NALPL2 in development stages and organs were observed, suggesting the difference of action phase and effector organ of NALPL1 and NALPL2. When the modulation of NALPL1 and NALPL2 in pathogen infection was analyzed, it was found that the two molecules were upregulated by both bacterial and viral infection. Overexpression of NALPL1 and NALPL2 resulted in significant inhibition for intracellular Edwardsiella tarda growth. Further studies demonstrated that NALPL1 and NALPL2 also contributed to protection against viral infection. These results demonstrate that both NALPL1 and NALPL2 are important intracellular proteins in host surveillance against both bacterial and viral infection. Interestingly, the expression of downstream signaling genes was not affected by the overexpression of NALPL1 or NALPL2, but NOD1 and MDA5 were upregulated by NALPL1 or NALPL2 overexpression, suggesting that they likely act in pathogen infection through the interaction with other PRRs.

Molecular cloning and functional characterization of peptidoglycan recognition protein 6 in grass carp Ctenopharyngodon idella.

Peptidoglycan recognition proteins (PGRPs) are pattern recognition molecules of innate immunity. In this study, a long-form PGRP, designated as gcPGRP6, was identified from grass carp Ctenopharyngodon idella. The deduced amino acid sequence of gcPGRP6 is composed of 464 residues with a conserved PGRP domain at the C-terminus. The gcPGRP6 gene consists of four exons and three introns, spacing approximately 2.7 kb of genomic sequence. Phylogenetic analysis demonstrated that gcPGRP6 is clustered closely with zebrafish PGLYRP6, and formed a long-type PGRP subfamily together with PGLYRP2 members identified in teleosts and mammals. Real-time PCR and Western blotting analyses revealed that gcPGRP6 is constitutively expressed in organs/tissues examined, and its expression was significantly induced in liver and intestine of grass carp in response to PGN stimulation and in CIK cells treated with lipoteichoic acid (LTA), polyinosinic polycytidylic acid (Poly I:C) and peptidoglycan (PGN). Immunofluorescence microscopy and Western blotting analyses revealed that gcPGRP6 is effectively secreted to the exterior of CIK cells. The over-expression of gcPGRP6 in CIK cells leads to the activation of NF-κB and the inhibition of intracellular bacterial growth. Moreover, cell lysates from CIK cells transfected with pTurbo-gcPGRP6-GFP plasmid display the binding activity towards Lys-type PGN from Staphylococcus aureus and DAP-type PGN from Bacillus subtilis. Furthermore, proinflammatory cytokine IL-2 and intracellular PGN receptor NOD2 had a significantly increased expression in CIK cells overexpressed with gcPGRP6. It is demonstrated that the PGRP6 in grass carp has a role in binding PGN, in inhibiting the growth of intracellular bacteria, and in activating NF-κB, as well as in regulating innate immune genes.