The development of catalytic enantioselective isocyanide‐based reactions is currently of great interest because the resulting products are valuable in organic synthesis, pharmacological chemistry, ...and materials science. This review assembles and comprehensively summarizes the recent achievements in this rapidly growing area according to the reaction types. Special attention is paid to the advantages, limitations, possible mechanisms, and synthetic applications of each reaction. In addition, a personal outlook on the opportunities for further exploration is given at the end.
Isocyanide‐based reactions: The development of catalytic enantioselective isocyanide‐based reactions is currently of great interest because the resulting products are valuable in organic synthesis, pharmacological chemistry, and materials science. This review assembles and comprehensively summarizes the recent achievements in this rapidly growing area according to the reaction types. Special attention is paid to the advantages, limitations, possible mechanisms, and synthetic applications of each reaction. In addition, a personal outlook on the opportunities for further exploration is given.
Tandem reactions of Pd‐catalyzed cross‐coupling of 3‐(2‐isocyanoethyl)indoles with diazoacetates and subsequent spirocyclization/Mannich‐type reaction have been developed to assemble polycyclic ...spiroindoline skeletons. Formation of spiroindolenines has been proven as the crucial step for the following Mannich‐type cyclization reaction. Accordingly, a novel approach on chiral phosphoric acid catalyzed Mannich‐type cyclization toward the formation of diastereomerically and enantiomerically enriched pentacyclic spiroindolines has been established. Moreover, the products of the reaction are versatile building blocks in synthetic chemistry, as demonstrated by the synthesis of the key framework of aspidosperma and kopsia alkaloids.
Polycyclic spiroindoline skeletons can be constructed through Pd‐catalyzed cross‐coupling of 3‐(2‐isocyanoethyl)indoles with diazoacetates and a subsequent spirocyclization/Mannich‐type cyclization cascade reaction. The products are versatile building blocks in synthetic chemistry, as demonstrated by the synthesis of the key framework of aspidosperma and kopsia alkaloids.
We have developed a palladium‐catalyzed cross‐coupling reaction of isocyanides with α‐diazoacetates to form active ketenimines and following a 1,4‐diazabicyclo2.2.2octane (DABCO) catalyzed ...aza‐Mannich type reaction with various 2‐mercaptoimidazoles for the synthesis of 1,3‐bis(β‐aminoacrylate)‐substituted 2‐mercaptoimidazole derivatives with structural diversity. In addition, the use of 1H‐benzodimidazol‐2‐ol as the reaction partner also allowed the formation of 1,3‐bis(β‐aminoacrylate)‐substituted 2‐benzimidazolinone derivatives with moderate yields (34–52%). In the aza‐Mannich reaction, the regioselective N‐attack rather than S‐attack or O‐attack at the electrophilic central carbon of ketenimines was observed. This tandem sequence is efficient since two C=C and two C−N bonds are consecutively created in one‐pot.
Extending Sadorsky (2010), this paper focuses on nonlinear effects of financial development and income on energy consumption. Utilizing five alternative measures of financial development, it employs ...a panel threshold regression approach to reexamine the effect of financial development and income on energy consumption. The analysis relies on a sample of 53 countries for the period 1999–2008, showing a single-threshold effect on energy consumption when private credit, domestic credit, value of traded stocks, and stock market turnover are used as financial development indicators. It implies that the sample can be split into two regimes: high income, and non-high income. Energy consumption increases with income in emerging market and developing economies, while in advanced economies energy consumption increases with income beyond a point at which the economy achieves a threshold level of income. In addition, in the non–high income regime, energy consumption increases with financial development when both private and domestic credit are used as financial development indicators. However, when the value of traded stocks and stock market turnover are used as financial development indicators, it slightly declines with financial development in advanced economies, especially in high-income countries, but increases in the higher income countries of emerging market and developing economies.
•Utilizing five alternative measures of financial development.•To split into two regimes: high income, and non-high income.•In non–high income, energy consumption increases with private and domestic credit.•In high income of advanced economies, it declines with stock market development.
Taiwan has strictly followed infection control measures to prevent spread of coronavirus disease. Meanwhile, nationwide surveillance data revealed drastic decreases in influenza diagnoses in ...outpatient departments, positivity rates of clinical specimens, and confirmed severe cases during the first 12 weeks of 2020 compared with the same period of 2019.
The receptor‐binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike (S) protein plays a central role in mediating the first step of virus infection to cause disease: virus ...binding to angiotensin‐converting enzyme 2 (ACE2) receptors on human host cells. Therefore, S/RBD is an ideal target for blocking and neutralization therapies to prevent and treat coronavirus disease 2019 (COVID‐19). Using a target‐based selection approach, we developed oligonucleotide aptamers containing a conserved sequence motif that specifically targets S/RBD. Synthetic aptamers had high binding affinity for S/RBD‐coated virus mimics (KD≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC50≈5 nM). Importantly, aptamers were able to neutralize S protein‐expressing viral particles and prevent host cell infection, suggesting a promising COVID‐19 therapy strategy.
Synthetic ssDNA aptamers containing a conserved sequence motif that specifically targets the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike have the capacity to neutralize the virus and prevent host cell infection in vitro, suggesting a new therapeutic approach to treat COVID‐19.
Tardigrades are remarkable for their ability to survive harsh stress conditions as diverse as extreme temperature and desiccation. The molecular mechanisms that confer this unusual resistance to ...physical stress remain unknown. Recently, tardigrade‐unique intrinsically disordered proteins have been shown to play an essential role in tardigrade anhydrobiosis. Here, we characterize the conformational and physical behaviour of CAHS‐8 from Hypsibius exemplaris. NMR spectroscopy reveals that the protein comprises an extended central helical domain flanked by disordered termini. Upon concentration, the protein is shown to successively form oligomers, long fibres, and finally gels constituted of fibres in a strongly temperature‐dependent manner. The helical domain forms the core of the fibrillar structure, with the disordered termini remaining highly dynamic within the gel. Soluble proteins can be encapsulated within cavities in the gel, maintaining their functional form. The ability to reversibly form fibrous gels may be associated with the enhanced protective properties of these proteins.
The conformational behaviour of an intrinsically disordered protein responsible for protecting tardigrades against extreme stress has been characterized. The protein assembles into fibres and fibrillar gels as a function of temperature and concentration. The disordered tails remain flexible within the gel cavities, which can encapsulate client proteins in their native state.
Catalytic tandem cyclization of ynamides has attracted considerable interest in organic synthesis because of its atom economy in the rapid formation of polycyclic compounds. However, examples on the ...construction of pentacyclic spiroindolines are quite scarce. Herein, we described a BiCl3‐mediated tandem cyclization reaction of tryptamine‐ynamides, which led to the formation of appealing pentacyclic spiroindoline scaffolds in moderate to excellent yields. In addition, such a reaction can lead to the divergent synthesis of tricyclic indole derivatives with moderate yields by engineering substrate structures. The synthetic utility of this methodology has also been demonstrated by further interesting transformations.
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