Escaping from Flatland: Antimalarial Activity of sp-Rich Bridged Pyrrolidine Derivatives.

We utilized synthetic photochemistry to generate novel sp-rich scaffolds and report the design, synthesis, and biological testing of a diverse series of amides based on the 1-(amino-methyl)-2-benzyl-2-aza-bicyclo[2.1.1]hexane scaffold.

Structural and Electronic Control of the Bidentate 1-(2-pyridyl)benzotriazole Ligand in Copper Chemistry with Application to Catalysis in the A Coupling Reaction.

The hybrid bidentate 1-(2-pyridyl)benzotriazole (pyb) ligand was introduced into 3d transition metal catalysis. Specifically, [Cu (OTf) (pyb) ]⋅2 CH CN (1) enables the synthesis of a wide range of propargylamines by the A coupling reaction at room temperature in the absence of additives. Experimental and high-level theoretical calculations suggest that the bridging N atom of the ligand imposes exclusive trans coordination at Cu and allows ligand rotation, while the N atom of the pyridine group modulates charge distribution and flux, and thus orchestrates structural and electronic precatalyst control permitting alkyne binding with simultaneous activation of the C-H bond via a transient Cu species.

Escaping from Flatland: Substituted Bridged Pyrrolidine Fragments with Inherent Three-Dimensional Character.

The pressure to deliver new medicines to the patient continues to grow along with increases in compound failure rate, thus putting the current R&D model at risk. Analysis has shown that increasing the three-dimensionality of potential drug candidates decreases the risk of failure and improves binding selectivity and frequency. For this reason many workers have taken a new look at the power of photochemistry as a means to generate novel sp rich scaffolds for use in drug discovery programs.

Shedding light on the use of Cu(ii)-salen complexes in the A coupling reaction.

One Cu(ii) complex, {Cu(ii)L} (1S), has been synthesised, in two high yielding steps under ambient conditions, and characterised by single-crystal X-Ray diffraction (SXRD), IR, UV-Vis, circular dichroism (CD), elemental analysis, thermogravimetric analysis (TGA) and electron spray ionization mass spectroscopy (ESI-MS). This air-stable compound enables the generation, at room temperature and in open-air, of twenty propargylamines, nine new, from secondary amines, aliphatic aldehydes and alkynes with a broad scope with yields up to 99%. Catalyst loadings can be as low as 1 mol%, while the recovered material retains its structural integrity and can be used up to 5 times without loss of its activity.

Escaping from Flatland: [2 + 2] Photocycloaddition; Conformationally Constrained sp-rich Scaffolds for Lead Generation.

Pressure on researchers to deliver new medicines to the patient continues to grow. Attrition rates in the research and development process present a significant challenge to the viability of the current model of drug discovery. Analysis shows that increasing the three-dimensionality of potential drug candidates decreases the risk of attrition, and it is for this reason many workers have taken a new look at the power of photochemistry, in particular photocycloadditions, as a means to generate novel sp-rich scaffolds for use in drug discovery programs.

The Synthesis of Waltherione F and Its Analogues with Modifications at the 2- and 3-Positions as Potential Antitrypanosomal Agents.

Chagas disease also know as American Trypanosomiasis (AT) is a tropical parasitic disease endemic in South America, is caused by Trypanosoma cruzi, which is transmitted by the blood-sucking insect vectors called triatomine bugs. Quinoline alkaloids from the root extract of Waltheria indica are known to possess antitrypanosomal activity. Waltherione F, one of those alkaloids, was synthesised in 5 steps in 11 % overall yield.