Visible-Light-Mediated Multicomponent Reaction for Secondary Amine Synthesis

The widespread presence of secondary amines in agrochemicals, pharmaceuticals, natural products, and small-molecule biological probes has inspired efforts to streamline the synthesis of molecules with this functional group. Herein, we...

Organometallic AIEgens for biological theranostics

The marriage of AIEgens and organometallic complexes has shown great potential in biological probes and photosensitizers.

Recent development and application of cyclometalated iridium(III) complexes as chemical and biological probes

Iridium complexes have been widely applied as molecular sensors because of their rich photophysical properties, including large Stokes shifts, long emission lifetimes, environment-sensitive emissions, and high luminescent quantum yields. In...

Recent advances on the synthesis of the antidepressant Paroxetine

: Paroxetine is a potent inhibitor of serotonin reuptake and is widely prescribed for the treatment of depression and other neurological disorders. The synthesis of paroxetine and the possibility to prepare derivatives with a specific substitution pattern that may allow their use as biological probes, is an attractive topic especially for medicinal chemists engaged in neurosciences research. Considering the extensive work that was developed in the last decade on the total synthesis of paroxetine, this review summarizes the most important contributions in this field, organized according to the reagent that was used as starting material. Most of the methods allowed to prepare paroxetine in 4-9 steps with an overall yield of 9-66%. Despite the progress made in this area, there is still room for improvement, searching for new eco-friendly and sustainable synthetic alternatives.

SuFEx-Enabled High-Throughput Medicinal Chemistry

<p>Optimization of small-molecule probes or drugs is a lengthy, challenging and resource-intensive process. Lack of automation and reliance on skilled medicinal chemists is cumbersome in both academic and industrial settings. Here, we demonstrate a high-throughput hit-to-lead process based on the biocompatible SuFEx click chemistry. A modest high-throughput screening hit against a bacterial cysteine protease SpeB was modified with a SuFExable iminosulfur oxydifluoride [RN=S(O)F2] motif, rapidly diversified into 460 analogs in overnight reactions, and the products directly screened to yield drug-like inhibitors with 300-fold higher potency. We showed that the improved molecule is drug-like and biologically active in a bacteria-host coculture. Since these reactions can be performed on a picomole scale to conserve reagents, we anticipate our methodology can accelerate the development of robust biological probes and drug candidates.</p>

SuFEx-Enabled High-Throughput Medicinal Chemistry

<p>Optimization of small-molecule probes or drugs is a lengthy, challenging and resource-intensive process. Lack of automation and reliance on skilled medicinal chemists is cumbersome in both academic and industrial settings. Here, we demonstrate a high-throughput hit-to-lead process based on the biocompatible SuFEx click chemistry. A modest high-throughput screening hit against a bacterial cysteine protease SpeB was modified with a SuFExable iminosulfur oxydifluoride [RN=S(O)F2] motif, rapidly diversified into 460 analogs in overnight reactions, and the products directly screened to yield drug-like inhibitors with 300-fold higher potency. We showed that the improved molecule is drug-like and biologically active in a bacteria-host coculture. Since these reactions can be performed on a picomole scale to conserve reagents, we anticipate our methodology can accelerate the development of robust biological probes and drug candidates.</p>