Palladium-Catalyzed Trans-Selective Synthesis of Spirocyclic Cyclobutanes Using α,α-Dialkylcrotyl- and Allylhydrazones.

Herein, we demonstrate the use of / mixtures of α,α-disubstituted crotylhydrazones to obtain spirocyclic vinylcyclobutanes in a diastereoselective fashion. We show 24 examples of a 1,1-insertion/4--trig tandem process to produce these motifs. Additionally, spirocyclic alkylidene cyclobutanes can be obtained by using α,α-disubstituted allylated hydrazones (11 examples).

Disruption of zinc (II) binding and dimeric protein structure of the XIAP-RING domain by copper (I) ions.

Modulation of metalloprotein structure and function via metal ion substitution may constitute a molecular basis for metal ion toxicity and/or metal-mediated functional control. The X-linked Inhibitor of Apoptosis Protein (XIAP) is a metalloprotein that requires zinc for proper structure and function. In addition to its role as a modulator of apoptosis, XIAP has been implicated in copper homeostasis.

Fine mapping and candidate gene analysis of a dravet syndrome modifier locus on mouse chromosome 11.

Pathogenic variants in SCN1A result in a spectrum of phenotypes ranging from mild febrile seizures to Dravet syndrome, a severe infant-onset epileptic encephalopathy. Individuals with Dravet syndrome have developmental delays, elevated risk for sudden unexpected death in epilepsy (SUDEP), and have multiple seizure types that are often refractory to treatment. Although most Dravet syndrome variants arise de novo, there are cases where an SCN1A variant was inherited from mildly affected parents, as well as some individuals with de novo loss-of-function or truncation mutations that presented with milder phenotypes.