A de novo Synthesis of Oxindoles from Cyclohexanone-Derived γ-Keto-ester Acceptors Using a Desaturative Amination–Cyclization Approach

Here we report a desaturative approach for oxindole synthesis. This method uses simple γ-ester-containing cyclohexanones and primary amine building blocks as coupling partners. A dual photoredox–cobalt manifold is used to generate a secondary aniline that, upon heating, cyclizes with the pendent ester functionality. The process operates under mild conditions and was applied to the modification of several amino acids, the blockbuster drug mexiletine, as well as the formation of dihydroquinolinones.

Recent Advances of Pharmaceutical Process Chemistry and Its Innovation in China: Part 1

This review article summarizes recent developments and innovations in China's pharmaceutical process chemistry over the last several decades. Case studies of dozens of blockbuster drug processes are presented, including bulk drugs, such as the over-the-counter medicine biotin, demonstrating China's substantial effort to green its pharmaceutical processes. Owing to the increasing stringent environmental regulations, Chinese chemists have invented several cutting-edge and eco-friendly synthetic methods that are beneficial to environmental protection. Applied to large-scale industrial production, these processes have a greatly reduced environmental footprint, promoting the sustainable development of global economy and health.

Improved, gram-scale synthesis of sildenafil in water using arylacetic acid as the acyl source in the pyrazolo[4,3-d]pyrimidin-7-one ring formation

An improved, gram-scale synthesis of the blockbuster drug sildenafil, used for the treatment of male erectile dysfunction, has been developed. Unlike the previous literature, the current method demonstrates the use...

Open science precision medicine in Canada: Points to consider

Open science can significantly influence the development and translational process of precision medicine in Canada. Precision medicine presents a unique opportunity to improve disease prevention and healthcare, as well as to reduce health-related expenditures. However, the development of precision medicine also brings about economic challenges, such as costly development, high failure rates, and reduced market size in comparison with the traditional blockbuster drug development model. Open science, characterized by principles of open data sharing, fast dissemination of knowledge, cumulative research, and cooperation, presents a unique opportunity to address these economic challenges while also promoting the public good. The Centre of Genomics and Policy at McGill University organized a stakeholders’ workshop in Montreal in March 2018. The workshop entitled “Could Open be the Yellow Brick Road to Precision Medicine?” provided a forum for stakeholders to share experiences and identify common objectives, challenges, and needs to be addressed to promote open science initiatives in precision medicine. The rich presentations and exchanges that took place during the meeting resulted in this consensus paper containing key considerations for open science precision medicine in Canada. Stakeholders would benefit from addressing these considerations as to promote a more coherent and dynamic open science ecosystem for precision medicine.

Mechanochemistryvs.solution growth: striking differences in bench stability of a cimetidine salt based on a synthetic method

A mechanochemically prepared solvated salt of an archetypal blockbuster drug exhibits significantly different bench stability to analogous material made in solution.