Ruthenium-Catalyzed Tandem C–H Fluoromethylation/Cyclization of N-Alkylhydrazones with CBr₃F: Access to 4-Fluoropyrazoles

Abstract

4-Fluoropyrazoles are accessible in a single step from readily available aldehyde-derived N-alkylhydrazones through double C-H fluoroalkylation with tribromofluoromethane (CBrF). RuCl(PPh) has been proven to be the most efficient catalyst for this transformation when compared to a range of other Cu-, Pd-, or Fe-based catalyst systems.

Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer

“…Although it has been suggested that Drp1 does not play a role during OSKM-induced somatic cell reprogramming [114], several reports indicate that this protein plays a key role in this process [78, 115, 116]. In this regard, we have observed an increase in both Drp1 total protein and Drp1-S579 phosphorylation during the stochastic phase of cell reprogramming.…”

“…ES cells present a fragmented mitochondrial morphology [65, 78]. Surprisingly, downregulation of growth factor erv1 -like ( Gfer ) in ES cells, which leads to an increase in Drp1 protein levels and mitochondrial fission rates, impairs pluripotency and induces apoptosis [79].…”

“…During early reprogramming, Erk1 and Erk2 are activated as a consequence of the downregulation of the Dusp6 protein phosphatase. Activated Erk1/2 phosphorylate Drp1-S579, which induces its recruitment to mitochondria and triggers mitochondrial fission during the stochastic phase of cell reprogramming [78] (Figure 2). In addition to Erk1/2, cyclin-dependent kinase 1 (Cdk1) could also participate in the phosphorylation of Drp1-S579 during early cell reprogramming [9].…”

“…Compared to somatic cells, ES cells show low levels of Mfn1/2 expression [78, 119]. Interestingly, Mfn1/2 knockout cells display a faster and higher efficiency of cell reprogramming due to an increase of mitochondrial fragmentation and cell proliferation.…”

“…Furthermore, Erk1/2-mediated phosphorylation of Mfn1 causes its inactivation [37]. Thus, in addition to increase mitochondrial fission through Drp1 phosphorylation [78], Erk1/2 activation during early cell reprogramming may inhibit mitochondrial fusion through Mfn1 phosphorylation (Figure 2). …”