Amphiphilic [pi]-allyliridium catalyzed nucleophilic and electrophilic allylation

Transition metal-catalyzed allylic substitution has emerged as a powerful method for stereoselective C-N bond formation. Chiral iridium-phosphoramidite complexes have proven especially effective as catalysts for regio- and enantioselective allylic amination, but are limited to aryl-substituted π-allyl electrophiles. With commercially available π-allyliridium C,O-benzoates, which are stable to air, water and SiO₂ chromatography, and are well known to catalyze allylic acetate mediated carbonyl allylation, highly regio- and enantioselective electrophilic allylation of aliphatic amines, primary and secondary aromatic or heteroaromatic amines were demonstrated. Furthermore, indoles and related azoles can also undergo the amination and generate enantiomerically enriched N-allyl indoles with completely N-selective and exclusive branched regioselectivity, which are an unmet challenge in this field. Moreover, indoles and related azoles are prevalent structural motifs in clinical candidates and FDA approved drugs, so these results also show the utility and importance of asymmetric allylic alkylation.Chemistr

Frequent Occurrence of Mitochondrial DNA Mutations in Barrett’s Metaplasia without the Presence of Dysplasia

BACKGROUND: Barrett's esophagus (BE) is one of the most common premalignant lesions and can progress to esophageal adenocarcinoma (EA). The numerous molecular events may play a role in the neoplastic transformation of Barrett's mucosa such as the change of DNA ploidy, p53 mutation and alteration of adhesion molecules. However, the molecular mechanism of the progression of BE to EA remains unclear and most studies of mitochondrial DNA (mtDNA) mutations in BE have performed on BE with the presence of dysplasia. METHODS/FINDINGS: Thus, the current study is to investigate new molecular events (Barrett's esophageal tissue-specific-mtDNA alterations/instabilities) in mitochondrial genome and causative factors for their alterations using the corresponding adjacent normal mucosal tissue (NT) and tissue (BT) from 34 patients having Barrett's metaplasia without the presence of dysplasia. Eighteen patients (53%) exhibited mtDNA mutations which were not found in adjacent NT. mtDNA copy number was about 3 times higher in BT than in adjacent NT. The activity of the mitochondrial respiratory chain enzyme complexes in tissues from Barrett's metaplasia without the presence of dysplasia was impaired. Reactive oxygen species (ROS) level in BT was significantly higher than those in corresponding samples. CONCLUSION/SIGNIFICANCE: High ROS level in BT may contribute to the development of mtDNA mutations, which may play a crucial role in disease progression and tumorigenesis in BE