Copper-Catalyzed Enantioselective [4π + 2σ] Cycloaddition of Bicyclobutanes with Nitrones.

The selective construction of bridged bicyclic scaffolds has garnered increasing attention because of their extensive use as saturated bioisosteres of arene in pharmaceutical industry. However, in sharp contrast to their racemic counterparts, assembling chiral bridged bicyclic structures in an enantioselective and regioselective manner remains challenging. Herein, we describe our protocol for constructing chiral 2-oxa-3-azabicyclo[3.

Enantioselective synthesis of chiral amides by carbene insertion into amide N-H bond.

Chiral amides are important structure in many natural products and pharmaceuticals, yet their efficient synthesis from simple amide feedstock remains challenge due to its weak Lewis basicity. Herein, we describe our study of the enantioselective synthesis of chiral amides by N-alkylation of primary amides taking advantage of an achiral rhodium and chiral squaramide co-catalyzed carbene N-H insertion reaction. This method features mild condition, rapid reaction rate (in all cases 1 min) and a wide substrate scope with high yield and excellent enantioselectivity.

Enantioselective Synthesis of Chiral Amides by a Phosphoric Acid Catalyzed Asymmetric Wolff Rearrangement.

The enantioselective addition of potent nucleophiles to ketenes poses challenges due to competing background reactions and poor stereocontrol. Herein, we present a method for enantioselective phosphoric acid catalyzed amination of ketenes generated from α-aryl-α-diazoketones. Upon exposure to visible light, the diazoketones undergo Wolff rearrangement to generate ketenes.

A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N-H Bonds.

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pK Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pK Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products.

Accessing Aliphatic Amines in C-C Cross-Couplings by Visible Light/Nickel Dual Catalysis.

A general aminoalkylation of aryl halides was developed, overcoming intolerance of free amines in nickel-mediated C-C coupling. This transformation features broad functional group tolerance and high efficiency. Taking advantage of the fast desilylation of α-silylamines upon single-electron transfer (SET) facilitated by carbonate, α-amino radicals are generated regioselectively, which then engage in nickel-mediated C-C coupling.

Catalytic Asymmetric Construction of a 1,2,4-Benzotriazepine Skeleton via Diastereo- and Enantioselective Decarboxylative [4 + 3] Cyclization.

We have developed a protocol for palladium-catalyzed decarboxylative [4 + 3] cycloaddition reactions between 4-vinyl benzoxazinanones and azomethine imines to generate moderate to good yields of structurally diverse 1,2,4-benzotriazepines bearing two stereogenic centers with good to excellent stereoselectivities. This protocol not only addresses the challenge of asymmetrically constructing compounds with a 1,2,4-benzotriazepine skeleton but also demonstrates the utility of decarboxylative cycloadditions for the synthesis of enantioenriched polycyclic compounds.

Synthesis of methylene cyclopropane-fused chromenes and dihydroquinolines by sequential [4 + 2]- and [1 + 2]-annulation.

A base promoted sequential [4 + 2]- and [1 + 2]-annulation of 2-hydroxychalcones or 2-tosylaminochalcones with prop-2-ynylsulfonium salts has been developed to give the corresponding methylene cyclopropane fused dihydroquinolines or chromenes in moderate to good yields. This transformation has advantage of wide substrate scope and functional group tolerance as well as excellent regioselectivity. Prop-2-ynylsulfonium salts act as both C2 and C1 synthons in the tandem processes.

Multifunctional Building Blocks Compatible with Photoredox-Mediated Alkylation for DNA-Encoded Library Synthesis.

DNA-encoded library (DEL) technology has emerged as a novel interrogation modality for ligand discovery in the pharmaceutical industry. Given the increasing demand for a higher proportion of C(sp)-hybridized centers in DEL platforms, a photoredox-mediated cross-coupling and defluorinative alkylation process is introduced using commercially available alkyl bromides and structurally diverse α-silylamines. Notably, no protecting group strategies for amines are necessary for the incorporation of a variety of amino-acid-based organosilanes, providing crucial branching points for further derivatization.

Highly Sensitive Detection of Uracil-DNA Glycosylase Activity Based on Self-Initiating Multiple Rolling Circle Amplification.

Sensitive detection of uracil-DNA glycosylase (UDG) activity is very important in the study of many fundamental biochemical processes and clinical applications. Here, we develop a novel assay for the detection of UDG activity by using the self-initiating multiple rolling circle amplification (SM-RCA) strategy. We first design a trigger probe modified with NH at its 3'-terminal and uracil base in the middle of sequence, which is complementary to a cyclized padlock probe.

Enhancement of the polymerase chain reaction by tungsten disulfide.

In this paper, we demonstrated that the polymerase chain reaction (PCR) could be dramatically enhanced by tungsten disulfide (WS). The results showed that the PCR efficiency could be increased with the addition of WS and at a lower annealing temperature, which simplified the design and operation of PCR. Moreover, PCR with WS showed better specificity and efficiency as compared with graphene oxide (GO) for a human genome DNA sample.

Multifunctional Oligonucleotide-Functionalized Conjugated Oligomer Nanoparticles for Targeted Cancer Cell Imaging and Therapy.

A novel and multifunctional oligonucleotide-functionalized conjugated oligomer nanoparticle (CON) is developed for effective cancer cell imaging and therapy by integration of fluorescence imaging, target recognition, photodynamic therapy (PDT), and chemotherapy. The CON itself possesses the high fluorescence emission efficiency for imaging and can generate reactive oxygen species for PDT. Due to its excellent biocompatibility, easy functional modification, and efficient drug loading and release ability, oligonucleotides enable the CON to be functionalized in many forms.