Rapid Construction of Vinyl Indomorphans by Rhenium Catalysis.

Here, an efficient route for accessing the vinylindomorphan skeleton is achieved by rhenium(I) catalysis. This transformation involves the condensation of indoles and alkyne-linked cyclohexanones, followed by intramolecular annulation to build the [3.3.1] bicyclic structure. This protocol complements the synthesis of the structurally complex heterocycles bearing a vinyl indole moiety. In addition, the selected products exhibited moderate cytotoxicity toward human A549 cells.

An Oxidant-Free and Mild Strategy for Quinazolin-4(3H)-One Synthesis via CuAAC/Ring Cleavage Reaction.

An oxidant-free and highly efficient synthesis of phenolic quinazolin-4(3H)-ones was achieved by simply stirring a mixture of 2-aminobenzamides, sulfonyl azides, and terminal alkynes. The intermediate N-sulfonylketenimine underwent two nucleophilic additions and the sulfonyl group eliminated through the power of aromatization. The natural product 2-(4-hydroxybenzyl)quinazolin-4(3H)-one can be synthesized on a large scale under mild conditions with this method.

CuX Dual Catalysis: Construction of Oxazolo[2,3-b][1,3]oxazines via a Tandem CuAAC/Ring Cleavage/[4+2+3] Annulation Reaction.

CuX as a simple dual catalyst strategy that promotes the tandem transformations of fused oxazolo[2,3-b][1,3]oxazines has been developed. Copper catalyzed terminal ynones, sulfonyl azides, and nitriles for the CuAAC/ring cleavage/[4+2] annulation reaction, while the halogen catalyzed ring cleavage and [2+3] annulation of oxiranes to form the final fused products. This study provides a four-component, one-pot strategy for synthesizing complex fused heterocycles from simple ingredients and expands the application of CuAAC in organic synthesis.

Copper-catalyzed three-component reaction to synthesize polysubstituted imidazo[1,2-a]pyridines.

An efficient three-component one-pot and operationally simple cascade of 2-aminopyridines with sulfonyl azides and terminal ynones is reported, providing a variety of polysubstituted imidazo[1,2-a]pyridine derivatives in moderate to excellent yields. In particular, the reaction goes a through CuAAC/ring-cleavage process and forms a highly active intermediate α-acyl-N-sulfonyl ketenimine with base free.

A simple and efficient copper-catalyzed three-component reaction to synthesize (Z)-1,2-dihydro-2-iminoquinolines.

A operationally simple synthesis of (Z)-1,2-dihydro-2-iminoquinolines that proceeds under mild conditions is achieved by copper-catalyzed reaction of 1-(2-aminophenyl)ethan-1-ones, sulfonyl azides and terminal ynones. In particular, the reaction goes through a base-free CuAAC/ring-opening process to obtain the Z-configured products due to hydrogen bonding.

Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity.

Development of novel anticancer therapeutic candidates is one of the key challenges in medicinal chemistry. Podophyllotoxin and its derivatives, as a potent cytotoxic agent, have been at the center of extensive chemical amendment and pharmacological investigation. Herein, a new series of podophyllotoxin-N-sulfonyl amidine hybrids (4a-4v, 5a-5f) were synthesized by a CuAAC/ring-opening procedure. All the synthesized podophyllotoxins derivatives were evaluated for in vitro cytotoxic activity against a panel of human lung (A-549) cancer cell lines. Different substituents', or functional groups' antiproliferative activities were discussed. The -CF3 group performed best (IC50: 1.65 µM) and exhibited more potent activity than etoposide. Furthermore, molecular docking and dynamics studies were also conducted for active compounds and the results were in good agreement with the observed IC50 values.

Organocatalytic Regiodivergent Ring Expansion of Cyclobutanones for the Enantioselective Synthesis of Azepino[1,2-a]indoles and Cyclohepta[b]indoles.

A regiodivergent organocatalytic enantioselective Michael addition/three-atom ring expansion sequence of electron-withdrawing group activated cyclobutanones with 2-nitrovinylindoles was developed. A series of azepino[1,2-a]indoles were obtained with exclusive regioselectivities and high diastereo- and enantioselectivities (up to >20:1 dr, 96% ee) with the application of the N1 nucleophilic site of the indole nucleus. Meanwhile, various cyclohepta[b]indoles could be accessed with high enantiopurity (up to 96% ee) through the Michael addition/boron-trifluoride-etherate-promoted indole C3-attack ring expansion process.

Enantioselective Construction of CF3-Containing Spirooxindole γ-Lactones via Organocatalytic Asymmetric Michael/Lactonization.

A highly enantioselective Michael/lactonization cascade reaction of 3-hydroxyoxindoles with 3-trifluoroethylidene oxindoles was developed. The use of a cinchona-derived squaramide catalyst is essential in achieving high diastereo- and enantioselectivities. This reaction represents the first example of intramolecular amide C-N bond cleavage and lactonization of 3-hydroxyoxindoles with 3-trifluoroethylidene oxindoles, which provides an efficient and convenient approach to diverse CF3-containing spirooxindole γ-lactones in high yields and good to excellent diastereo- and enantioselectivities.

Joint Magnetic Calibration and Localization Based on Expectation Maximization for Tongue Tracking.

BACKGROUND: Tongue tracking, which helps researchers gain valuable insights into speech mechanism, has many applications in speech therapy and language learning. The wireless localization technique, which involves tracking a small magnetic tracer within the 3-D oral space, provides a low cost and convenient approach to capture tongue kinematics. In practice, this technique requires accurate calibration of three-axial magnetic sensors used in the tracking system. The data-driven calibration depends on the trajectories of magnetic tracer and the ambient noise, which may change across time and space. METHODS: In this paper, we model the kinematics of tracer movement and the noisy magnetic measurements in a Bayesian framework, then present a joint calibration and localization (JCL) algorithm based on expectation maximization (EM), where the unscented Rauch-Tung-Striebel smoother is employed for tracer localization and the curvilinear search algorithm is applied for sensor calibration. RESULTS: Based on measurements conducted on our tongue tracking system with a small magnetic tracer (diameter: 6.05 mm, thickness: 1.25 mm, residual induction: 14 800 G), the JCL algorithm achieves averaged root mean square error of 0.45 mm for tracer position estimation and for tracer orientation estimation, which are significantly lower than those of the separate calibration and localization algorithms. CONCLUSION: These results show that JCL can help improve the localization accuracy of this system. SIGNIFICANCE: A potentially high precision tongue tracking method is demonstrated.

Asymmetric Synthesis of 3,4-Dihydroquinolin-2-ones via a Stereoselective Palladium-Catalyzed Decarboxylative [4 + 2]- Cycloaddition.

An efficient, palladium-catalyzed, decarboxylative [4 + 2]-cycloaddition of 4-vinyl benzoxazinanones with carboxylic acids has been developed with the employment of P-chiral monophosphorus ligand BI-DIME, affording a series of structurally diverse 3,4-dihydroquinolin-2-ones bearing two contiguous stereogenic centers in moderate to good yields with good to excellent stereoselectivities.

Magnetic implants in the tongue for assistive technologies: Tests of migration; oromotor function; and tissue response in miniature pigs.

OBJECTIVE: Uncertain biological consequences of titanium-magnet (Ti-mag) tongue implants constrain application of the Tongue Drive System (TDS), a brain-tongue-computer interface for individuals with severe physical impairment. Here we describe oromotor function and tongue tissue response following Ti-Mag implantation and explantation in the miniature pig, an animal model with a tongue similar in size to humans. DESIGN: A 1.8×6.2mm Ti-mag tracer was implanted into the anterior tongue in five Yucatan minipigs. X-rays were taken immediately and >six days after implantation to evaluate tracer migration. In three minipigs, the tracer was explanted >16days after implantation. Twenty-five days post-explantation, tongue tissue was harvested and processed for histological and immunohistochemical (IHC) markers of healing. In two minipigs tissue markers of healing were evaluated post-mortem following >12days implantation. Drink cycle rate (DCR) was characterized to determine the impact of procedures on oromotor function. RESULTS: Neither implantation (N=5) nor explantation (N=3) changed DCR. X-rays revealed minimal tracer migration (N=4, 0-4mm). By histology and IHC a robust capsule was present two weeks post-implantation with limited fibrosis. Explantation produced localized fibrosis and limited muscle remodeling. CONCLUSIONS: These findings suggest the safety of Ti-mag anterior tongue implants for assistive technologies in humans.