Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems.

An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD-NH2 ) and PdII complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ6 -protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD-NH2 catalyst and the branched chain of the substrate, hydrogen-bonding interactions between the N-H of the enamine motif and the C=O of the directing group MQ, and the counterion of the PdII complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.

Transformation of the shape and shrinking the size of acid-resistant metal-organic frameworks (MOFs) for use as the vehicle of oral proteins.

The oral delivery of protein-based drugs is of great significance, but faces various obstacles, including the deactivation of proteins by the low pH in the stomach and the high concentration of protease, poor transport through intestinal bio-barriers, etc. Herein, we present an acid-resistant metal-organic framework (MOF), NU-1000, in which insulin (Ins, a model protein) was loaded with high capacity (Ins@NU-1000) through the pseudo second-order kinetic model and Langmuir isotherm model. Ins@NU-1000 protects Ins from deactivation in the stomach acid environment and releases it in the intestine through the transformation of the micro-sized rod particles into spherical nanoparticles. Interestingly, the rod particles exhibit long-term retention in the intestine, and Ins is efficiently transported by the shrunk nanoparticles through intestinal bio-barriers and released into the blood, resulting in significant oral hypoglycemic effects (lasting more than 16 h after a single oral administration). Our findings demonstrate that switching the physical properties of the delivery vehicle, such as the shape and size, can contribute to the success of oral protein administration.

Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.

Primary liver cancer is a severe and complex disease, leading to 800000 global deaths annually. Emerging evidence suggests that inflammation is one of the critical factors in the development of hepatocellular carcinoma (HCC). Patients with viral hepatitis, alcoholic hepatitis, and steatohepatitis symptoms are at higher risk of developing HCC. However, not all inflammatory factors have a pathogenic function in HCC development. The current study describes the process and mechanism of hepatitis development and its progression to HCC, particularly focusing on viral hepatitis, alcoholic hepatitis, and steatohepatitis. Furthermore, the roles of some essential inflammatory cytokines in HCC progression are described in addition to a summary of future research directions.

Oxyallyl cation promoted dearomative semipinacol rearrangement: a facile stereodivergent synthesis of spiro-indolines with contiguous quaternary centers.

A novel oxyallyl cation promoted semipinacol rearrangement of indole-type allylic alcohols was disclosed for the stereodivergent synthesis of spiro-indolines. A variety of spiro-indolines were obtained with moderate to good yields. Three contiguous stereocenters, two of which are vicinal quaternary centers, were effectively formed with good diastereoselectivity. It is worth noting that two diastereoisomers of rearranged products can be readily achieved by easily regulating the reaction conditions. This method may provide an applicable approach for the synthesis of natural indole alkaloids.

Dynamics of above- and belowground responses of silver birch saplings and soil gases to soil freezing and waterlogging during dormancy.

Winter precipitation and soil freeze-thaw events have been predicted to increase in boreal regions with climate change. This may expose tree roots to waterlogging (WL) and soil freezing (Fr) more than in the current climate and therefore affect tree growth and survival. Using a whole-tree approach, we studied the responses of silver birch (Betula pendula Roth.) saplings, growing in mineral soil, to 6-week Fr and WL in factorial combinations during dormancy, with accompanying changes in soil gas concentrations. Physiological activation (dark-acclimated chlorophyll fluorescence and chlorophyll content index) and growth of leaves and shoot elongation and stem diameter growth started earlier in Fr than NoFr (soil not frozen). The starch content of leaves was temporarily higher in Fr than NoFr in the latter part of the growing season. Short and long root production and longevity decreased, and mortality increased by soil Fr, while there were no significant effects of WL. Increased fine root damage was followed by increased compensatory root growth. At the beginning of the growing season, stem sap flow increased fastest in Fr + WL, with some delay in both NoWL (without WL) treatments. At the end of the follow-up growing season, the hydraulic conductance and impedance loss factor of roots were higher in Fr than in NoFr, but there were no differences in above- and belowground biomasses. The concentration of soil carbon dioxide increased and methane decreased by soil Fr at the end of dormancy. At the beginning of the growing season, the concentration of nitrous oxide was higher in WL than in NoWL and higher in Fr than in NoFr. In general, soil Fr had more consistent effects on soil greenhouse gas concentrations than WL. To conclude, winter-time WL alone is not as harmful for roots as WL during the growing season.

Enantioselective Synthesis of 3,3'-Disubstituted 2-Amino-2'-hydroxy-1,1'-binaphthyls by Copper-Catalyzed Aerobic Oxidative Cross-Coupling.

A challenging direct asymmetric catalytic aerobic oxidative cross-coupling of 2-naphthylamine and 2-naphthol, using a novel CuI /SPDO system, has been successfully developed for the first time. Enantioenriched 3,3'-disubstituted NOBINs were achieved and could be readily derived to divergent chiral ligands and catalysts. This reaction features high enantioselectivities (up to 96 % ee) and good yields (up to 80 %). The DFT calculations suggest that the F-H interactions between CF3 of L17 and H-1,8 of 2-naphthol, and the π-π stacking between the two coupling partners could play vital roles in the enantiocontrol of this cross-coupling reaction.

Copper-Complex-Catalyzed Asymmetric Aerobic Oxidative Cross-Coupling of 2-Naphthols: Enantioselective Synthesis of 3,3'-Substituted C1 -Symmetric BINOLs.

A novel chiral 1,5-N,N-bidentate ligand based on a spirocyclic pyrrolidine oxazoline backbone was designed and prepared, and it coordinates CuBr in situ to form an unprecedented catalyst that enables efficient oxidative cross-coupling of 2-naphthols. Air serves as an external oxidant and generates a series of C1 -symmetric chiral BINOL derivatives with high enantioselectivity (up to 99 % ee) and good yield (up to 87 %). This approach is tolerant of a broader substrates scope, particularly substrates bearing various 3- and 3'-substituents. A preliminary investigation using one of the obtained C1 -symmetric BINOL products was used as an organocatalyst, exhibiting better enantioselectivity than the previously reported organocatalyst, for the asymmetric α-alkylation of amino esters.

Waterlogging and soil freezing during dormancy affected root and shoot phenology and growth of Scots pine saplings.

Soil waterlogging is predicted to increase in the future climate in boreal regions due to increased precipitation. Snowmelt periods in winter may also become more common and further increase the amount of water in soil. It is not well known how waterlogging and soil freezing during winter affect the physiology, phenology and growth of trees. Our aim was to study the below- and aboveground responses of Scots pine (Pinus sylvestris L.) saplings to waterlogging (WL) in frozen (Fr) and unfrozen (NoFr) soils in a growth chamber experiment. The soil was either -2 °C or +2 °C and either waterlogged or not in a split-plot design for 6 weeks during dormancy, with similar air conditions in all treatments, which were Fr + WL, NoFr + WL, Fr + NoWL and NoFr + NoWL. Needles showed a shift towards a deeper dormancy in frozen than unfrozen soil in terms of chlorophyll fluorescence (Fv/Fm), water potential and apoplastic electrical resistance. In spring, initiation of shoot elongation started earlier if the soil was frozen during dormancy. In Fr + WL, initiation of root growth was delayed by 20 days compared with other treatments; after that, the root growth peaked at the same time as needle elongation. Needles remained smaller in Fr + WL than in the other treatments, indicating that roots formed a strong sink for carbon. Shoot and root biomass were not negatively affected by waterlogging if the soil remained unfrozen. In Fr + WL, survival and growth capacity of new terminal and whorl buds, the number of bud scales and the number of dwarf shoots were reduced. We conclude that soil freezing on sites prone to waterlogging should be considered in management of boreal forests, especially in the face of predicted climate change.

Double SO2 Insertion into 1,7-Diynes Leading to Functionalized Naphtho[1,2-c]thiophene 2,2-dioxides.

A novel metal-free double SO2 insertion/multicomponent bicyclization cascade of benzene-linked 1,7-diynes has been established by treatment with aryldiazonium tetrafluoroborates and DABCO-bis(sulfur dioxide) under redox-neutral conditions, providing a range of dual sulfone-containing naphtho[1,2-c]thiophene 2,2-dioxides with generally high stereoselectivity. The reaction pathway is proposed to proceed through the sequence of arylsulfonyl-radical-induced 6-exo-dig/5-endo-trig bicyclization, H-abstraction, and diazotization.

Stereoselective synthesis of sulfonated 1-indenones via radical-triggered multi-component cyclization of ß-alkynyl propenones.

New radical-triggered multi-component cyclizations of ß-alkynyl propenones have been developed, leading to 50 examples of sulfonated 1-indenones with generally good yields and high levels of stereoselectivity. The oxidant-free azosulfonylation of ß-alkynyl propenones with aryldiazonium salts and DABSO was realized under the neutral-redox conditions where TBHP enabled the direct selenosulfonylation of ß-alkynyl propenones by combining sulfinic acids and diphenyl diselenide. This protocol features a broad substrate scope, high functional group tolerance and mild reaction conditions.

Silver-mediated radical 5-exo-dig cyclization of 2-alkynylbenzonitriles: synthesis of phosphinylated 1-indenones.

A new silver-mediated 5-exo-dig cyclization of 2-alkynylbenzonitriles with disubstituted phosphine oxide and H2O has been developed. The reaction enables multiple bond-forming events including C-P, C-C and C-O bonds under atmospheric conditions, leading to the concise and direct formation of 28 examples of phosphorus-containing 1-indenones with generally good yields.

Ag-Catalyzed difluorohydration of ß-alkynyl ketones for diastereoselective synthesis of 1,5-dicarbonyl compounds.

A new catalytic difluorohydration of ß-alkynyl ketones using NFSI as the fluorinating reagent has been established, diastereoselectively furnishing a range of structurally diverse difluoride 1,5-dicarbonyl products through C(sp3)-H fluorination. Notably, the sterically encumbered t-butyl functionality located at the α-position of the carbonyl group of substrates 1 showed excellent diastereoselectivity (up to >99 : 1 dr). The reaction enabled multiple bond-forming events including two C(sp3)-F formation through Ag-catalysis to provide a highly efficient and practical method toward difluoride 1,5-dicarbonyls, some of which were successfully converted into difluorinated isoquinolines.

Metal-free benzannulation of 1,7-diynes towards unexpected 1-aroyl-2-naphthaldehydes and their application in fused aza-heterocyclic synthesis.

A novel I2-mediated benzannulation of 1,7-diyne-involved 1,4-oxo-migration was established, providing a range of unexpected 1-aroyl-2-naphthaldehydes with a 1,4-dicarbonyl unit. The resulting 1-aroyl-2-naphthaldehydes were successfully applied in the synthesis of benzo[e]isoindol-3-ones and benzo[e]benzo[4,5]imidazo[2,1-a]isoindoles using aromatic amines and benzene-1,2-diamines as nucleophiles, respectively. The mechanisms for the formation of these compounds were proposed.

Photosynthesis, nutrient accumulation and growth of two Betula species exposed to waterlogging in late dormancy and in the early growing season.

Increased risk of soil waterlogging in winter and spring at northern latitudes will potentially affect forest production in the future. We studied gas exchange, chlorophyll content index, chlorophyll fluorescence, nutrient concentration and biomass accumulation in 1-year-old silver (Betula pendula Roth) and pubescent birch (Betula pubescens Ehrh.) seedlings. We hypothesized that B. pubescens has different physiological mechanisms that make it tolerate waterlogging better than B. pendula. The treatments were: (i) no waterlogging throughout the experiment; (ii) 4-week waterlogging during dormancy (dormancy waterlogging 'DW'); (iii) 4-week waterlogging during the early growing season (growth waterlogging 'GW'); and (iv) 4-week DW followed by 4-week GW during the early growing season ('DWGW'). Stomatal conductance and light-saturated net assimilation rate were reduced by GW in both species, and in B. pubescens also by DW. However, recovery was seen during the follow-up growing season. In B. pendula, DW, GW and DWGW temporarily resulted in reduced stem biomass, and GW and DWGW caused reduced leaf biomass. In B. pubescens, the stem biomass was decreased in GW and DWGW. Leaf nitrogen (N) and phosphorus (P) concentrations were generally low, and increased by GW, while potassium, calcium, magnesium and to some extent, boron and zinc concentrations decreased in both species and additionally manganese in B. pendula. The increases in N and P are mostly due to a concentration effect due to smaller leaf biomass, yet suggest that their uptake was not impaired. The decreases in cation concentrations are likely to be connected to impaired root functioning, which was not yet fully recovered from GW. We conclude that morphological acclimation to waterlogging of the leaves and roots rather than photosynthesis explains why B. pubescens is able to grow better in wetter areas than B. pendula.

Waterlogging in late dormancy and the early growth phase affected root and leaf morphology in Betula pendula and Betula pubescens seedlings.

The warmer winters of the future will increase snow-melt frequency and rainfall, thereby increasing the risk of soil waterlogging and its effects on trees in winter and spring at northern latitudes. We studied the morphology of roots and leaves of 1-year-old silver birch (Betula pendula Roth) and pubescent birch (Betula pubescens Ehrh.) seedlings exposed to waterlogging during dormancy or at the beginning of the growing season in a growth-chamber experiment. The experiment included 4-week dormancy (Weeks 1-4), a 4-week early growing season (Weeks 5-8) and a 4-week late growing season (Weeks 9-12). The treatments were: (i) no waterlogging, throughout the experiment ('NW'); (ii) 4-week waterlogging during dormancy (dormancy waterlogging 'DW'); (iii) 4-week waterlogging during the early growing season (growth waterlogging 'GW'); and (iv) 4-week DW followed by 4-week GW during the early growing season ('DWGW'). Dormancy waterlogging affected the roots of silver birch and GW the roots and leaf characteristics of both species. Leaf area was reduced in both species by GW and DWGW. In pubescent birch, temporarily increased formation of thin roots was seen in root systems of GW seedlings, which suggests an adaptive mechanism with respect to excess soil water. Additionally, the high density of non-glandular trichomes and their increase in DWGW leaves were considered possible morphological adaptations to excess water in the soil, as was the constant density of stem lenticels during stem-diameter growth. The higher density in glandular trichomes of DWGW silver birch suggests morphological acclimation in that species. The naturally low density of non-glandular trichomes, low density of stem lenticels in waterlogged seedlings and decrease in root growth seen in DWGW and DW silver birch seedlings explain, at least partly, why silver birch grows more poorly relative to pubescent birch in wet soils.

Metal-Free Radical Haloazidation of Benzene-Tethered 1,7-Enynes Leading to Polyfunctionalized 3,4-Dihydroquinolin-2(1H)-ones.

A new cascade three-component haloazidation of benzene-tethered 1,7-enynes for the formation of biologically interesting azidylated 3,4-dihydroquinolin-2(1H)-ones has been achieved under mild and metal-free conditions using TMSN3 as a N3 source and NIS (or NBS or NCS) as a halogen source. The reaction pathway involves in situ-generated azidyl radical-triggered α,ß-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in successive multiple bond-forming events, including carbon-nitrogen, carbon-carbon, and carbon-halogen bonds to rapidly construct complex heterocyclic molecules. Furthermore, the resulting products would be useful building blocks in the discovery of lead compounds and other biologically interesting N3-containing heterocycles.

A new cascade halosulfonylation of 1,7-enynes toward 3,4-dihydroquinolin-2(1H)-ones via sulfonyl radical-triggered addition/6-exo-dig cyclization.

A new cascade three-component halosulfonylation of 1,7-enynes for efficient synthesis of densely functionalized 3,4-dihydroquinolin-2(1H)-ones has been established from readily accessible arylsulfonyl hydrazides and NIS (or NBS). The reaction pathway involves in situ-generated sulfonyl radical-triggered α,ß-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in continuous multiple bond-forming events including C-S, C-C and C-I (or C-Br) bonds to rapidly build up molecular complexity.

Catalytic Arylsulfonyl Radical Triggered 1,7-Enyne Bicyclizations.

A new metal-free bicyclization reaction of 1,7-enynes anchored by α,ß-conjugates with arylsulfonyl radicals generated in situ from sulfonyl hydrazides has been established using tert-butyl hydroperoxide and tetrabutylammonium iodide. The reactions occurred through sulfonylation/6-exo-dig/6-exo-trig bicyclization/in situ desulfonylation/5-exo-trig cyclization/alkyl or alkenyl migration cascade mechanism to give benzo[j]phenanthridines regioselectively.

[Research advances in mathematical model of coniferous trees cold hardiness].

Plant cold hardiness has complicated attributes. This paper introduced the research advances in establishing the dynamic models of coniferous trees cold hardiness, with the advantages and disadvantages of the models presented and the further studies suggested. In the models established initially, temperature was concerned as the only environmental factor affecting the cold hardiness, and the concept of stationary level of cold hardiness was introduced. Due to the obvious prediction errors of these models, the stationary level of cold hardiness was modeled later by assuming the existence of an additive effect of temperature and photoperiod on the increase of cold hardiness. Furthermore, the responses of the annual development phases for cold hardiness to environment were considered. The model researchers have paid more attention to the additive effect models, and run some experiments to test the additivity principle. However, the research results on Scots pine (Pinus sylvestris) indicated that its organs did not support the presumption of an additive response of cold hardiness by temperature and photoperiod, and the interaction between environmental factors should be taken into account. The mathematical models of cold hardiness need to be developed and improved.