Atroposelective Brønsted Acid-Catalyzed Photocyclization to Access Chiral N-Aryl Quinolones with Low Rotational Barriers.

Herein, a novel route to atropisomeric N-aryl quinolones with low rotational barriers is demonstrated, leveraging a dual photochemical/organocatalytic approach to the required ring closure in up to 94% yield and up to >99% ee. The use of a continuous flow system allows for impurity suppression and enables rapid scale-up to a decagram scale.

Telescoped Process to Manufacture 6,6,6-Trifluorofucose via Diastereoselective Transfer Hydrogenation: Scalable Access to an Inhibitor of Fucosylation Utilized in Monoclonal Antibody Production.

IgG1 monoclonal antibodies with reduced glycan fucosylation have been shown to improve antibody-dependent cellular cytotoxicity (ADCC) by allowing more effective binding of the Fc region of these proteins to T cells receptors. Increased in vivo efficacy in animal models and oncology clinical trials has been associated with the enhanced ADCC provided by these engineered mAbs. 6,6,6-Trifluorofucose (1) is a new inhibitor of fucosylation that has been demonstrated to allow the preparation of IgG1 monoclonal antibodies with lower fucosylation levels and thus improve the ADCC of these proteins. A new process has been developed to support the preparation of 1 on large-scale for wide mAb manufacture applications. The target fucosylation inhibitor (1) was synthesized from readily available d-arabinose in 11% overall yield and >99.5/0.5 dr (diastereomeric ratio). The heavily telescoped process includes seven steps, two crystallizations as purification handles, and no chromatography. The key transformation of the sequence involves the diastereoselective preparation of the desired trifluoromethyl-bearing alcohol in >9/1 dr from a trimethylsilylketal intermediate via a ruthenium-catalyzed tandem ketal hydrolysis-transfer hydrogenation process.

Effects of cyclic strain on rat tail tenocytes.

Cyclical mechanical strain is considered an important component in flexor tendon cell activation to prevent adhesions and enhance the healing process after tissue injury or surgery, but the biochemical events associated with this remain unclear. To address this, we examined the effects of cyclic tension on the expression of hyaluronic acid, an important lubricant and signal transducer in tendon, on its receptor (CD44), and on total glycosaminoglycan content in rat tail derived tendon fibroblasts in vitro. Tenocytes were plated on fibronectin coated silastic membranes and the cultures were held static or subjected to vacuum induced deformation for a period of 5 min once every 8 h as a model of cyclic mechanical stress. After 24 h medium and cell layers were collected for analyses by product specific ELISA, Western blot, and colorimetric dye-binding assays. Strained tenocytes produced a nearly two-fold increase in hyaluronic acid and a greater than 60% increase in CD44, but had an insignificant effect on total glycosaminoglycan content. Our results predict that high levels of strain may therefore rapidly enhance the expression of hyaluronic acid and cause, albeit still unresolved, downstream effects on CD44 activation, to influence tendon cell activity and enhance the process of tendon repair.

The influence of plastic surgery "reality TV" on cosmetic surgery patient expectations and decision making.

BACKGROUND: The aim of this study was to survey first-time patients seeking cosmetic surgery and examine what role "reality TV" played in their perception of the risks and benefits of surgery and their overall decision-making process. METHODS: Information on demographics, television viewing patterns, and patients' self-assessed plastic surgery knowledge was collected from 42 patients. They were asked how similar they believed the shows were to real life and what degree of influence the shows had on their decision to pursue cosmetic surgery. Patients were then divided into groups by program viewing intensity. RESULTS: Fifty-seven percent of patients were "high-intensity" viewers of plastic surgery reality television shows. When compared with low-intensity viewers, high-intensity viewers believed themselves to be more knowledgeable about plastic surgery (p < 0.05) and believed the shows were more similar to real life (p < 0.05). Overall, four of five patients reported that television influenced them to pursue a cosmetic surgery procedure, with nearly one-third feeling "very much" or "moderately" influenced. CONCLUSIONS: Plastic surgery reality television plays a significant role in cosmetic surgery patient perceptions and decision making. Patients who regularly watched one or more reality television show reported a greater influence from television and media to pursue cosmetic surgery, felt more knowledgeable about cosmetic surgery in general, and felt that plastic surgery reality television was more similar to real life than did low-intensity viewers.

A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid.

A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.

The AMPA receptor subunit GluR1 regulates dendritic architecture of motor neurons.

The morphology of the mature motor neuron dendritic arbor is determined by activity-dependent processes occurring during a critical period in early postnatal life. The abundance of the AMPA receptor subunit GluR1 in motor neurons is very high during this period and subsequently falls to a negligible level. To test the role of GluR1 in dendrite morphogenesis, we reintroduced GluR1 into rat motor neurons at the end of the critical period and quantitatively studied the effects on dendrite architecture. Two versions of GluR1 were studied that differed by the amino acid in the "Q/R" editing site. The amino acid occupying this site determines single-channel conductance, ionic permeability, and other essential electrophysiologic properties of the resulting receptor channels. We found large-scale remodeling of dendritic architectures in a manner depending on the amino acid occupying the Q/R editing site. Alterations in the distribution of dendritic arbor were not prevented by blocking NMDA receptors. These observations suggest that the expression of GluR1 in motor neurons modulates a component of the molecular substrate of activity-dependent dendrite morphogenesis. The control of these events relies on subunit-specific properties of AMPA receptors.