Covalent Organic Frameworks Based Photoenzymatic Nano-reactor for Asymmetric Dynamic Kinetic Resolution of Secondary Amines.

Bio-catalysis represents a highly efficient and stereoselective method for the synthesis of valuable chiral compounds, however, the poor stability and limited reaction types of free enzymes restrict their wide application in industrial production. In this work, to overcome these problems, a multifunctional photoenzymatic nanoreactor CALB@COF-Ir was developed through the encapsulation of Candida antarctica lipase B (CALB) in a photosensitive covalent organic framework COF-Ir. This bio-nanocluster serves as efficient catalysts in asymmetric dynamic kinetic resolution (DKR) of secondary amines to give a series of chiral amines in high yields (up to 99 %) and enantioselectivities (up to 99 % ee). The well-designed COF-Ir not only acts as safety cover to prevent CALB from deactivation but promotes racemization of secondary amines via photo-induced hydrogen atom transfer (HAT) process. Photoelectric characterization and TDDFT calculation revealed that (ppy)2Ir units in COF-Ir play crucial role in this photocatalytic system which enhance its photo-redox properties through facilitating the separation between photoelectrons (e-) and holes (h+). Furthermore, the heterogeneous photoenzymatic nanoreactor could be recycled for five rounds with slight decline of catalytic reactivity.

Design, Synthesis, and Antifungal Activities of Novel Potent Fluoroalkenyl Succinate Dehydrogenase Inhibitors.

The development of new fungicide molecules is a crucial task for agricultural chemists to enhance the effectiveness of fungicides in agricultural production. In this study, a series of novel fluoroalkenyl modified succinate dehydrogenase inhibitors were synthesized and evaluated for their antifungal activities against eight fungi. The results from the in vitro antifungal assay demonstrated that compound 34 exhibited superior activity against Rhizoctonia solani with an EC50 value of 0.04 µM, outperforming commercial fluxapyroxad (EC50 = 0.18 µM) and boscalid (EC50 = 3.07 µM). Furthermore, compound 34 showed similar effects to fluxapyroxad on other pathogenic fungi such as Sclerotinia sclerotiorum (EC50 = 1.13 µM), Monilinia fructicola (EC50 = 1.61 µM), Botrytis cinerea (EC50 = 1.21 µM), and also demonstrated protective and curative efficacies in vivo on rapeseed leaves and tomato fruits. Enzyme activity experiments and protein-ligand interaction analysis by surface plasmon resonance revealed that compound 34 had a stronger inhibitory effect on succinate dehydrogenase compared to fluxapyroxad. Additionally, molecular docking and DFT calculation confirmed that the fluoroalkenyl unit in compound 34 could enhance its binding capacity with the target protein through p-π conjugation and hydrogen bond interactions.

Pyrene-Based D-A Molecules as Efficient Heterogeneous Catalysts for Visible-Light-Induced Aerobic Organic Transformations.

In this work, an efficient visible light promoted aerobic dehydro-coupling of amines, oxidation of thioethers and hydroxylation of arylboronic acids under benign conditions by using pyrene-based donor-acceptor (D-A) conjugated organic molecules was described. Donor-acceptor structure influences their π-conjugation and band gap a lot, and thereby enhances their visible light absorption ability, single electron transfer and oxidative behaviors. Alkynyl units in PS-IV play a crucial role in the catalyst which could serve as electron transferring bridge to strengthen electron delocalization, thus facilitating the single electron transfer from photosensitizer to substrates, and making it an efficient ⋅O2 - generator. While PS-III without alkynyl units tends to produce 1 O2 . Therefore, these molecules can serve as efficient catalysts for different kinds of visible-light-induced aerobic organic reactions. More importantly, the simply structured molecule is insoluble and stable in various solvents, and thus could be recycled as heterogeneous catalyst for many rounds with slight catalytic activity degradation. Besides, large scale (1 mol) reaction of benzylamine coupling proceeded smoothly under the standard conditions.

Chemical characterization, absolute configuration and optical purity of (1S)-(+)- and (1R)-(-)-10-camphorsulfonic acid.

Comprehensive chemical characterization for two isomers of camphorsulfonic acid (CSA), occasionally used in the manufacture of active pharmaceutical ingredients (APIs), was performed by nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectroscopy in negative electrospray ionization mode and gas chromatography/mass spectrometry (GC/MS) in electron ionization mode. Electronic circular dichroism (ECD) spectra together with quantum chemical calculations using time-dependent density functional theory (TD-DFT) were used to assign the stereochemistry for CSA for the first time and these assignments were then confirmed by single-crystal X-ray diffraction. As crystals were grown under the same conditions of high supersaturation using a mixed solvent without water removal, the crystal structures of the two enantiomers contained one ordered molecule of water in the asymmetric unit. The crystals of the (+)-enantiomer have a 1S,4R configuration and the H atom of the sulfonic acid group combines with the water molecule to form a hydronium ion, namely, hydronium (1S,4R)-(7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate, H3O+·C10H15O4S-. The crystals of the (-)-enantiomer have a 1R,4S configuration. The determination of the optical purity of CSA using NMR spectroscopy with a chiral solvating agent, (1R,2R)-1,2-diphenylethane-1,2-diamine, and GC/MS with a chiral column has been well explored. The results showed that the examined samples of these two isomers of CSA proved to be enantiomerically pure. In particular, for (1R)-(-)-10-camphorsulfonic acid, this is, to our knowledge, the first description on its spectral characterization in a scientific context.

Synthesis of bioactive fluoropyrrolidines via copper(i)-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides.

Chiral pyrrolidinyl units are important building blocks in biologically active natural products and drugs, and the development of efficient methods for the synthesis of diverse structured pyrrolidine derivatives is of great importance. Meanwhile, incorporating fluorine containing groups into small molecules often changes their activities to a great extent due to the special physicochemical properties of fluorine atoms. Herein, we report an efficient route to obtain enantioenriched 3,3-difluoro- and 3,3,4-trifluoropyrrolidinyl derivatives by Cu(i)-catalysed enantioselective 1,3-dipolar cycloaddition of azomethine ylides with less active 1,1-difluoro- and 1,1,2-trifluorostyrenes. A series of new fluorinated pyrrolidines have been prepared in high yields (up to 96%) and with excellent stereoselectivities (up to >20 : 1 dr and 97% ee), and these unique structural blocks could be readily introduced into some natural compounds and pharmaceuticals. Additionally, antifungal activity investigation against four common plant fungi showed that some products possess general and high biological activities; comparison with the low antifungal activities of corresponding nonfluorinated compounds revealed that the fluorine atoms at the pyrrolidinyl rings play a crucial role in the antifungal activity.