The catalytic conversion of chemical feedstocks into products of medicinal and agricultural value is a key theme across modern synthetic chemistry. As 1,3-dienes are readily available from industrial ...cracking processes, there is great interest in the development of sustainable methods for the functionalization of these simple molecules. Although initial developments in this field have required precious-transition-metal catalysts, there has been a push toward the use of inexpensive, nontoxic, and more abundant copper catalysts to promote functionalization. This Perspective covers the many developments in the area of copper-catalyzed functionalization of 1,3-dienes, in particular hydrofunctionalization, borofunctionalization, and difunctionalization (e.g., diamination).
Sulfonium salts are playing an increasingly significant role in contemporary organic synthesis. In particular, the generation of radicals from sulfonium salts is a fundamental process in Nature and ...has been the subject of investigation for over 50 years. However, general synthetic methods that use sulfonium salts as radical precursors are rare. The advent of photoredox catalysis has triggered an upsurge of interest in the radical chemistry of sulfonium salts and this review surveys recent applications of aryl‐ and alkylsulfonium salts in light‐mediated, radical C−C bond formation.
Trifluoromethyl sulfoxides are a new class of trifluoromethylthiolating reagent. The sulfoxides engage in metal‐free C−H trifluoromethylthiolation with a range of (hetero)arenes. The method is also ...applicable to the functionalization of important compound classes, such as ligand derivatives and polyaromatics, and in the late‐stage trifluoromethylthiolation of medicines and agrochemicals. The isolation and characterization of a sulfonium salt intermediate supports an interrupted Pummerer reaction mechanism.
May I interrupt? Taking advantage of the interrupted Pummerer reaction, trifluoromethyl sulfoxides engage in the metal‐free C−H trifluoromethylthiolation of (hetero)arenes, including drug molecules and natural products. This new class of trifluoromethylthiolating reagent exploits a new strategy for trifluoromethylthiolation in which sulfonium salts are assembled and selectively deconstructed.
We report a transition-metal-free synthesis of benzofurans from benzothiophenes and phenols that exploits the unique reactivity of sulfoxides. Through a sequence involving an interrupted Pummerer ...reaction and 3,3 sigmatropic rearrangement, phenols can be combined with readily accessible yet synthetically unexplored benzothiophene S-oxides to provide C3-arylated benzofuran products. The products from this approach can undergo subsequent functionalization to gain access to a range of important benzofuran derivatives.
An efficient, enantio‐ and diastereoselective, copper‐catalyzed coupling of imines, 1,3‐enynes, and diborons is reported. The process shows broad substrate scope and delivers complex, chiral ...homopropargyl amines; useful building blocks on the way to biologically‐relevant compounds. In particular, functionalized homopropargyl amines bearing up to three contiguous stereocenters can be prepared in a single step.
The enantio‐ and diastereoselective, copper‐catalyzed three‐component coupling of imines, 1,3‐enynes, and diborons delivers complex, chiral homopropargyl amines; useful building blocks on the way to biologically‐ and medicinally‐relevant compounds. In particular, functionalized homopropargyl amines bearing up to three contiguous stereocenters can be prepared in a single step.
Candida albicans, an opportunistic fungal pathogen, is a significant cause of human infections, particularly in immunocompromised individuals. Phenotypic plasticity between two morphological ...phenotypes, yeast and hyphae, is a key mechanism by which C. albicans can thrive in many microenvironments and cause disease in the host. Understanding the decision points and key driver genes controlling this important transition and how these genes respond to different environmental signals is critical to understanding how C. albicans causes infections in the host. Here we build and analyze a Boolean dynamical model of the C. albicans yeast to hyphal transition, integrating multiple environmental factors and regulatory mechanisms. We validate the model by a systematic comparison to prior experiments, which led to agreement in 17 out of 22 cases. The discrepancies motivate alternative hypotheses that are testable by follow-up experiments. Analysis of this model revealed two time-constrained windows of opportunity that must be met for the complete transition from the yeast to hyphal phenotype, as well as control strategies that can robustly prevent this transition. We experimentally validate two of these control predictions in C. albicans strains lacking the transcription factor UME6 and the histone deacetylase HDA1, respectively. This model will serve as a strong base from which to develop a systems biology understanding of C. albicans morphogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Due to their ubiquity in nature and frequent use in organic electronic materials, benzothiophenes are highly sought after. Here we set out an unprecedented procedure for the formation of ...benzothiophenes by the twofold vicinal C−H functionalization of arenes that does not require metal catalysis. This one‐pot annulation proceeds through an interrupted Pummerer reaction/3,3‐sigmatropic rearrangement/cyclization sequence to deliver various benzothiophene products. The procedure is particularly effective for the rapid synthesis of benzothiophenes from non‐prefunctionalized polyaromatic hydrocarbons (PAHs).
Thio‐fusion: Benzothiophenes are accessed from non‐prefunctionalized arenes in a one‐pot sequence involving an interrupted Pummerer reaction, 3,3‐sigmatropic rearrangement, and cyclization. The process does not require metals, proceeds by twofold C−H functionalization, and can be used to achieve the straightforward π‐extension of polyaromatic hydrocarbons.
A multicomponent copper-catalyzed enantio- and regioselective borocyanation of 1-aryl-1,3-butadienes has been developed. The method provides access to functionalized allylic nitriles in up to 90% ...yield and 94% ee and thus overcomes some of the long-standing problems associated with the enantioselective insertion of cyano groups into unsaturated organic molecules. Both boron and cyano functionalities can be used as handles for selective manipulation.
Summary
Over the past several years, novel modified clotting factor concentrates (CFCs) have been introduced into practice and are now widely prescribed in the countries where they are licensed. ...These products allow for less frequent infusions of CFC, thereby providing improved convenience and/or higher trough levels. They have been extensively studied for prophylaxis, episodic treatment of bleeding and for surgical prophylaxis. One issue that has emerged regarding the clinical application of these products revolves around the measurement of infused CFC in the clinical coagulation laboratory. Recent studies have demonstrated significant problems with the measurement of correct FVIII/IX levels following infusion of novel CF VIII/IX concentrates. The source of this problem appears to be related to the tremendous variability of the APTT reagents that are used in the one‐stage clotting assay, the most commonly used assay for determining factor levels. More specifically, the issue is related to the type of activator used in the reagents. Depending on the combination of the CFC and the APTT activator, the observed results may be either under‐ or overestimated to degrees that would be clinically relevant. Recommendations based on a review of published information regarding the potential for incorrect measurements of factor VIII/IX levels following infusion of recently developed, novel factor VIII/IX CFCs are presented for the clinician to use in clinical practice.
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