Pd-Catalyzed Enantioselective Tandem C-C Bond Activation/Cacchi Reaction between Cyclobutanones and o-Ethynylanilines.

A palladium-catalyzed asymmetric tandem C-C bond activation/Cacchi reaction between cyclobutanones and o-ethynylanilines was reported. The transient chiral σ-alkylpalladium species generated via enantioselective C(sp3)-C(sp2) bond activation of cyclobutanones promotes cyclization of o-ethynylanilines, leading to one-carbon-tethered chiral indanone-substituted indoles. Two C-C bonds and one C-N bond are created with concomitant formation of an all-carbon quaternary stereocenter. Furthermore, a chiral C2-aryl axis can be created in 2,3-disubstituted indole moiety, leading to indanone-substituted indoles with both central and axial stereogenic elements.

Tooth discoloration and the effects of internal bleaching on the novel endodontic filling material SavDen® MTA.

BACKGROUND/PURPOSE: Mineral trioxide aggregate (MTA) was widely used in endodontic therapy as bioceramic material. Although MTA has high biocompatibility, it may lead to tooth discoloration. The aim of this study was to investigate the discoloration of two different bioceramic materials and the effects of internal bleaching. METHODS: Thirty single-canal mandibular premolars were extracted and randomly assigned to three groups (n = 10), white ProRoot® MTA, SavDen® MTA and a control group. Endodontic access opening, cleaning and shaping were performed, then the teeth were obturated using the two bioceramic materials. Tooth color was recorded at baseline, day 1, and 1, 2, 4, 6, 8, 12, 16, and 24 weeks after treatment. At the end of 24 weeks, sodium perborate was used to perform internal bleaching. Tooth color was recorded at 1, 2, and 6 weeks subsequently. Teeth were measured using a DeguDent® spectrophotometer, and data were transformed into Commission Internationale de l'Eclairage (CIE) L∗a∗b∗ system. RESULTS: Teeth treated with white ProRoot® MTA showed significant color change and decrease in L∗ value. Internal bleaching leaded to decrease of the ΔE∗ value for all three groups and increase in the L∗ value. There was no difference in tooth discoloration between SavDen® MTA and the control group after obturation and internal bleaching. CONCLUSION: In terms of visual perception, white ProRoot® MTA tends to cause black and blue discoloration. SavDen® MTA, formulated with calcium lactate gluconate, could be used to reduce tooth discoloration in endodontic treatment.

Enantioselective palladium/copper-catalyzed C-C σ-bond activation synergized with Sonogashira-type C(sp3)-C(sp) cross-coupling alkynylation.

The Sonogashira-type cross-coupling reaction is one of the most significant alkynylation transformations in organic chemistry. However, highly enantioselective alkynylation via the Sonogashira-type cross-coupling reaction is rather limited, mainly due to the difficulties in matching the stereoselective induction of chiral ligands with the combinational behavior of Pd/Cu-based bimetallic catalysts. We herein report novel enantioselective palladium/copper-catalyzed alkyl alkynylation of cyclobutanones with terminal alkynes via tandem C-C bond activation/Sonogashira-type cross coupling reaction, in which a novel chiral TADDOL-derived phosphoramidite ligand bearing fluorine and silicon-based bulky groups simplified as TFSi-Phos is found to be an efficient ligand for both C(sp2)-C(sp3) bond cleavage and new C(sp3)-C(sp) bond formation. A wide range of chiral alkynylated indanones bearing an all-carbon quaternary stereocenter are obtained efficiently with up to 97.5 : 2.5 er.

KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: a meta-analysis of 22 studies.

Epidemiologic studies have evaluated the association between KRAS mutations and resistance to the treatment of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, results were inconclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic computerized searches of the PubMed and Medline databases (up to Jun 30, 2009) were performed. A total of 22 studies were included in the final meta-analysis, consisting of 1470 NSCLC patients, of whom 231 had KRAS mutations (16%). Current or former smokers had a higher frequency of KRAS mutations than never smokers (25% versus 6%; OR=4.36; P<0.01). Mutations were more common among adenocarcinoma than other histologies (26% versus 16%; OR=1.98; P<0.01). The objective response rate (ORR) of NSCLC patients with mutant KRAS was 3% (6/210), whereas the ORR of NSCLC patients with wild-type KRAS was 26% (287/1125). The overall pooled RR for ORR was 0.29 (95% CI: 0.18-0.47; P<0.01). Subgroup analyses were conducted on the basis of ethnicity and study treatment, all the results were not materially altered and did not draw different conclusions, indicating that our results were robust. In summary, this meta-analysis suggests that KRAS mutations may represent negative predictive biomarkers for tumor response in NSCLC patients treated with EGFR-TKIs. However, due to a mutually exclusive relationship between KRAS and EGFR mutation and no difference in survival between KRAS mutant/EGFR wild-type and KRAS wild-type/EGFR wild-type NSCLC, the clinical usefulness of KRAS mutation as a selection marker for EGFR-TKIs sensitivity in NSCLC is limited.