Verubulin

A nonconventional oxidative denitrogenative radical transacetylation method for the chemoselective N-acetylation of primary and secondary aryl/heteroaryl amines using acetohydrazide as a new source of acetyl radical has been discussed. This method, conducted under mild, transition-metal-free conditions in water, offers significant advantages over existing acetylation strategies, which largely rely on harsh reagents such as acetic anhydride, acetyl chloride, or enzyme catalysts. The process utilizes environmentally friendly reagents, namely, tert-butyl hydroperoxide (TBHP) and tert-butyl ammonium iodide (TBAI), to generate acetyl radicals through the oxidative cleavage of acetohydrazide, enabling efficient and selective N-acetylation of a wide variety of amines, including those bearing other sensitive functional groups. Control experiments with radical scavengers confirmed the in situ generation of the acetyl radical, providing strong evidence for the proposed mechanism. Importantly, this protocol demonstrates excellent scalability with successful application in the synthesis and late-stage functionalization of pharmaceutical compounds and advanced drug intermediates. The method not only expands the toolkit for amine functionalization but also offers a sustainable and scalable approach for industrial applications in drug discovery and development.

Microtubules (MTs), as structural components of the cytoskeleton, are vital for axonal transport, information processing, and signaling within the brain. Disruption of MT integrity has been associated with neurological disorders, including alcohol use disorder (AUD). This study used positron emission tomography (PET) imaging with the radiotracer [¹¹C]MPC-6827 to investigate alcohol-induced changes in MT dynamics in a nonhuman primate model of AUD. Dynamic PET scans (0-120 min) were conducted in male cynomolgus monkeys (n = 4) before and after ∼7 months of ethanol self-administration (EtOH SA). Quantitative analysis of standardized uptake values and time-activity curves demonstrated a consistent decrease in [¹¹C]MPC-6827 uptake across multiple brain regions, particularly in the amygdala, globus pallidus, and substantia innominata. Statistically significant reductions in tracer uptake were observed in early scan windows (15 and 30 min), suggesting compromised MT integrity due to chronic EtOH SA. These findings provide compelling evidence that chronic alcohol consumption induces significant changes in microtubule dynamics, potentially contributing to pathological processes underlying AUD.