Site-selective chlorination of pyrrolic heterocycles by flavin dependent enzyme PrnC.

Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. While there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation have been lacking.

Direct arene trifluoromethylation enabled by promiscuous activity of fungal laccase.

Laccase from was found to oxidize non-phenolic arenes and enable the trifluoromethylation of arenes in the presence of generated CF radicals at a catalyst loading as low as 0.0034%. The biocatalytic trifluoromethylation proceeded under mild conditions and could increase the yield by up to 12 fold, compared to the control.

Further Characterization of Fungal Halogenase RadH and Its Homologs.

RadH is one of the flavin-dependent halogenases that has previously exhibited promising catalytic activity towards hydroxycoumarin, hydroxyisoquinoline, and phenolic derivatives. Here, we evaluated new functional homologs of RadH and expanded its specificities for the halogenation of non-tryptophan-derived, heterocyclic scaffolds. Our investigation revealed that RadH could effectively halogenate hydroxyquinoline and hydroxybenzothiophene.

Toward Resolving the Resveratrol Conundrum: Synthesis and Pharmacokinetic Evaluation of BCP-Resveratrol.

Over the last few decades, resveratrol has gained significance due to its impressive array of biological activities; however, its true potential as a drug has been severely constrained by its poor bioavailability. Indeed, several studies have implicated this bioavailability trait as a major road-block to resveratrol's potential clinical applications. To mitigate this pharmacokinetic issue, we envisioned a tactical bioisosteric modification of resveratrol to bicyclo[1.

Radical fluorination powered expedient synthesis of 3-fluorobicyclo[1.1.1]pentan-1-amine.

Exploration of novel chemical space, a modern trend in medicinal chemistry, is heavily reliant on synthetic access to new and interesting building blocks. In this direction, the following work describes an expedient synthesis of one such moiety, 3-fluorobicyclo[1.1.

3-Deazaneplanocin A and neplanocin A analogues and their effects on apoptotic cell death.

3-Deazaneplanocin A (DzNep) is a potential epigenetic drug for the treatment of various cancers. DzNep has been reported to deplete histone methylations, including oncogenic EZH2 complex, giving rise to epigenetic modifications that reactivate many silenced tumor suppressors in cancer cells. Despite its promise as an anticancer drug, little is known about the structure-activity relationships of DzNep in the context of epigenetic modifications and apoptosis induction.

A new route to bicyclo[1.1.1]pentan-1-amine from 1-azido-3-iodobicyclo[1.1.1]pentane.

From a medicinal chemistry perspective, bicyclo[1.1.1]pentan-1-amine (1) has served as a unique and important moiety.

Cell-based proteome profiling using an affinity-based probe (AfBP) derived from 3-deazaneplanocin A (DzNep).

3-Deazaneplanocin A (DzNep), a global histone methylation inhibitor, has attracted significant interest in epigenetic research in recent years. The molecular mechanism of action and the cellular off-targets of DzNep, however, are still not well-understood. Our aim was to develop novel DzNep-derived small-molecule probes suitable to be used in live mammalian cells for identification of potential cellular targets of DzNep under physiologically relevant settings.