ABSTRACT
We report a phosphine-mediated direct ß-acylation of α,ß-unsaturated 1,3-diketones with acyl chlorides and a base. Functionalized furanones were also prepared by the reaction of cinnamic acid and acyl chloride according to our protocol via ß-acylation. Our studies revealed that α,ß-unsaturated 1,3-diketones with an electron-donating group at the second position favor the formation of ß-acylated products, whereas those with oxygen, such as anhydrides, favor furanones via an unprecedented C-acylation/cyclization sequence.
ABSTRACT
Pulmonary administration is a noninvasive drug delivery method that, in contrast to systemic administration, reduces drug dosage and possible side effects. Numerous testing models, such as impingers and impactors, have previously been developed to evaluate the fate of inhaled drugs. However, such models are limited by the lack of information regarding several factors, such as pulmonary morphology and breathing motion, which are required to fully interpret actual inhaled-drug deposition profiles within the human respiratory tract. In this study, a spontaneous breathing-lung model that integrates branched morphology and deformable alveolar features was constructed using a multilayered fabrication technology to mimic the complex environment of the human lower respiratory tract. The developed model could emulate cyclic and spontaneous breathing motions to inhale and exhale aerosols generated by a nebulizer under diseaselike conditions. Results of this research demonstrate that aerosols (4.2 µm) could reach up to the deeper lung regions (generation 19 of the branched lung structure) within the obstructivelike model, whereas lesser penetration (generation 17) was observed when using the restrictivelike model. The proposed breathing-lung model can serve as a testing platform to provide a comprehensive understanding of the pharmacokinetics of pulmonary drugs within the lower lungs.
ABSTRACT
A highly efficient and chemoselective one-pot protocol for the diversity-oriented synthesis of two types of coumarin-based formal cross-coupling adducts, furo[3,2-c]coumarins and 3-benzofuranyl chromenones, is described. Key attributes of the methodology are an initial chemoselective acylation of functionalized phosphorus zwitterions and a subsequent chemoselective intramolecular Wittig reaction that preferentially resulted in one of the two coumarin derivatives in high yield, depending on relative reactivities and the addition sequence of the acylating agents.
ABSTRACT
The patients with end-stage of renal disease (ESRD) need to take oral phosphate binder. Traditional phosphate binders may leave the disadvantage of aluminum intoxication or cardiac calcification. Herein, Mg-Fe-Cl hydrotalcite-like nanoplatelet (HTln) is for the first time characterized as potential oral phosphate binder, with respect to its phosphorus uptake capacity in cow milk and cellular cytotoxicity. A novel method was developed for synthesizing the Mg-Fe-Cl HTln powder in different Mg(2+): Fe(3+) ratios where the optimization was 2.8:1. Addition of 0.5 g Mg-Fe-Cl HTln in cow milk could reduce its phosphorus content by 40% in 30 min and by 65% in 90 min. In low pH environment, the Mg-Fe-Cl HTln could exhibit relatively high performance for uptaking phosphorus. During a 90 min reaction of the HTln in milk, no phosphorus restoration occurred. In-vitro cytotoxicity assay of Mg-Fe-Cl HTln revealed no potential cellular cytotoxicity. The cells that were cultured in the HTln extract-containing media were even more viable than cells that were cultured in extract-free media (blank control). The Mg-Fe-Cl HTln extract led to hundred ppm of Mg ion and some ppm of Fe ion in the media, should be a positive effect on the good cell viability.
