Synthesis of Succinonitrile Derivatives by Homocoupling from Cyanohydrin Derivatives with a Low-Valent Titanium Reagent.

A method is described for synthesizing succinonitrile derivatives bearing alkyl or aryl substituents from cyanohydrin derivatives using low-valent titanium. The active species in this reaction is proposed to be a resonance hybrid of the TiIV nitrile enolate and TiIII alkyl radical.

Synthesis of Methylenebicyclo[3.2.1]octanol by a Sm(II)-Induced 1,2-Rearrangement Reaction with Ring Expansion of Methylenebicyclo[4.2.0]octanone.

Direct conversion of methylenebicyclo[4.2.0]octanone to methylenebicyclo[3.2.1]octanol by a Sm(II)-induced 1,2-rearrangement with ring expansion of the methylenecyclobutane is described. Three conditions were optimized to allow the adaptation of this approach to various substrates. A rearrangement mechanism is proposed involving the generation of a ketyl radical and cyclopentanation by ketyl-olefin cyclization, followed by radical fragmentation and subsequent protonation.

Polysulfides protect SH-SY5Y cells from methylglyoxal-induced toxicity by suppressing protein carbonylation: A possible physiological scavenger for carbonyl stress in the brain.

The formation of advanced glycation end products (AGEs) is associated with various neurological disorders, such as Alzheimer's disease, Parkinson's disease and schizophrenia. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is known to be a major precursor for AGEs in modified proteins. Thus, a scavenger of MG might provide beneficial effects by suppressing the accumulation of AGEs and the occurrence of diseases induced by carbonyl stress. Meanwhile, polysulfides, one of the typical bound sulfur species, are oxidized forms of hydrogen sulfide (H2S) and may play a variety of roles in the brain. Herein, we assessed the scavenging ability of polysulfides against neuronal carbonyl stress induced by MG. First, we showed that polysulfides could protect differentiated (df)-SH-SY5Y cells from MG-induced cytotoxicity. When cells were pretreated with polysulfides, MG-induced cytotoxicity was attenuated with a rapid decrease in intracellular MG levels. Moreover, we found that polysulfides significantly suppressed the formation of MG-modified proteins in df-SH-SY5Y cells. Although polysulfide treatment increased endogenous GSH levels in the neuronal cells, its effects on MG-induced cytotoxicity were not affected by GSH concentration. Our results demonstrated that polysulfides had the direct potentials to protect neuronal cells against MG separate to the enzymatic detoxification system that required GSH.

A simple convenient synthesis of L-[4-13C]glutamine.

L-[4-(13)C]Glutamine was synthesized from sodium [2-(13)C]acetate in 12 steps and 18% overall yield. A Wittig reaction of (R)-benzyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate and ethyl 2-(triphenylphosphoranylidene)[2-(13)C]acetate prepared from D-serine and sodium [2-(13)C]acetate, respectively, gave (4S)-4-(2-ethoxycarbonyl[2-(13)C]vinyl)-2,2-dimethyloxazolidine-3-carboxylic acid α,ß-isopropylidene group, oxidation of the resulting hydroxyl group to a carboxyl group and transamidation of the ester moiety gave L-N-Cbz-[4-(13)C]glutamine (Cbz = benzyloxycarbonyl). Finally, removal of the Cbz group gave L-[4-(13)C]glutamine. L-[4-(13)C]Glutamine can be prepared in fewer steps and higher yield by this method compared with previously reported methods.