Electrochemical Azo-free Mitsunobu-type Reaction.

The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by-products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu-type reaction, which features azo-free alcohol activation and broad substrate scope. This user-friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee's. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple-step synthesis of a drug candidate.

Recombinant Mouse ß-Defensin 3 Protects against Coxsackievirus B3-Induced Myocarditis in Mice.

OBJECTIVES: To investigate the protective effect of recombinant mouse ß-defensin 3 (rMBD3) against coxsackievirus B3 (CVB3)-induced myocarditis in mice. METHODS: CVB3-infected HeLa cells were treated with rMBD3, and the titer of CVB3 and the proliferative activities of the cells were determined. CBV3-infected BALB/c mice were divided into five groups: rMBD3 high (5 mg/kg/day, q.d.), rMBD3 low (2.5 mg/kg/day, q.d.), ribavirin (10 mg/kg/day, q.d.), normal control, and myocarditis control. On days 5 and 12 after treatment, 3 mice from each group were sacrificed and serum lactate dehydrogenase, creatine kinase-MB isozyme, and tumor necrosis factor-α levels were determined. The heart index and the inflammation of myocardial tissue were also assessed. On day 5, the CVB3 50% tissue culture infective dose (TCID50) values of heart tissues were measured. RESULTS: rMBD3 inhibited the replication of CVB3 and protected HeLa cells from infection. rMBD3 reduced the CVB3 titer markedly and inhibited the pathological reaction of cardiac myocytes to viral myocarditis. Treatment with rMBD3 improved the cell survival rate and reduced the cardiac index. CONCLUSION: rMBD3 was demonstrated to possess anti-CVB3 activity in vivo and in vitro.

Electrochemical Difunctionalization of Styrenes via Chemoselective Oxo-Azidation or Oxo-Hydroxyphthalimidation.

Atom- and step-economic oxo-azidation and oxo-hydroxyphthalimidation of styrenes have been developed under mild electrolytic conditions, respectively. Various valuable alpha-azido or hydroxyphthalimide aromatic ketones were synthesized efficiently from readily available styrenes, azides, and N-hydroxyphthalimides. Mechanism studies show that two different pathways involved in these two transformations.