Highly (E)-Selective Trisubstituted Alkene Synthesis by Low-Valent Titanium-Mediated Homolytic Cleavage of Alcohol C-O Bond.

Ti-mediated homolytic C-O bond cleavage was useful for cascade radical-ionic reactions. Benzyl alcohols treated with TiCl4(col) (col = 2,4,6-collidine) and Mn powder generated the corresponding benzyl radicals; in addition, their reaction with 2-carboxyallyl acetates and the subsequent elimination of the acetoxy group yielded α,ß-unsaturated carbonyl compounds with exclusive (E)-stereoselectivity. The simplicity of the procedure and its wide substrate scope represent a solution to the drawbacks associated with the reactions.

Atrophy of White Adipose Tissue Accompanied with Decreased Insulin-Stimulated Glucose Uptake in Mice Lacking the Small GTPase Rac1 Specifically in Adipocytes.

Insulin stimulates glucose uptake in adipose tissue and skeletal muscle by inducing plasma membrane translocation of the glucose transporter GLUT4. Although the small GTPase Rac1 is a key regulator downstream of phosphoinositide 3-kinase (PI3K) and the protein kinase Akt2 in skeletal muscle, it remains unclear whether Rac1 also regulates glucose uptake in white adipocytes. Herein, we investigated the physiological role of Rac1 in white adipocytes by employing adipocyte-specific rac1 knockout (adipo-rac1-KO) mice. Subcutaneous and epididymal white adipose tissues (WATs) in adipo-rac1-KO mice showed significant reductions in size and weight. Actually, white adipocytes lacking Rac1 were smaller than controls. Insulin-stimulated glucose uptake and GLUT4 translocation were abrogated in rac1-KO white adipocytes. On the other hand, GLUT4 translocation was augmented by constitutively activated PI3K or Akt2 in control, but not in rac1-KO, white adipocytes. Similarly, to skeletal muscle, the involvement of another small GTPase RalA downstream of Rac1 was demonstrated. In addition, mRNA levels of various lipogenic enzymes were down-regulated in rac1-KO white adipocytes. Collectively, these results suggest that Rac1 is implicated in insulin-dependent glucose uptake and lipogenesis in white adipocytes, and reduced insulin responsiveness due to the deficiency of Rac1 may be a likely explanation for atrophy of WATs.

Structure-activity relationship between Zn2+-chelated alkylated poly(1-vinylimidazole) and gene transfection.

The structure-activity relationship between Zn2+-chelated alkylated poly(1-vinylimidazole) (PVIm) and gene transfection has been demonstrated. From a chemical structure perspective, ethylated PVIm (PVIm-Et) chelated the most Zn2+ ions compared to methylated PVIm (PVIm-Me) and butylated PVIm (PVIm-Bu). The resulting Zn2+-chelated PVIm-Et formed more stable complexes with plasmid DNA complex than non-chelated PVIm-Et. From a biological activity perspective, the Zn2+-chelated PVIm-Et delivered the highest amount of Zn2+ ions inside the cell, corresponding to the highest gene transfection. These results suggest that PVIm-Et is the optimal sequence for the chelation of Zn2+ ions to enhance the gene transfection activity. The structure-activity relationship in this study is expected to offer a unique molecular design for drug/gene delivery systems.