Impact of Magnesium(II) on Beryllium Fluorides in Solutions Studied by 19F NMR Spectroscopy

Beryllium fluorides are widely used in protein phosphorylation studies to get stable transition state analogs or near attack conformers, which has attracted much attention. BeF₃^? is one of the optimal phosphoryl (PO₃^?) analogs for its identical geometry and charge, and Mg²⁺ naturally participates in the phosphoryl binding in biological systems. In solutions, BeF₃^? coexists with other beryllium fluorides (BeF₄^2?, BeF₂ and BeF⁺) and magnesium fluorides, and there are equilibriums between these species. In this article, ¹⁹F NMR spectroscopy was applied to the investigation of the impact of magnesium(II) on beryllium fluorides. It has been found that when Mg²⁺ was introduced into the solutions, the chemical shifts, the intensities and the line widths of ¹⁹F signals of various beryllium fluoride complexes were changed. After ionic strength correction, these effects were remarkable only for BeF₄^2? and BeF₃^?, especially BeF₄^2?, when the concentration of the fluoride ion is relatively low. Mechanism of the effects is proposed which involves ion pair formation between Mg²⁺ and beryllium fluorides.     

Ring Opening of N‐Sulfonyl Aziridines by Amines in Silica‐Water

Ring opening reactions of N‐sulfonyl aziridines by primary and secondary amines in silica gel (SG)‐water system were achieved, which provided a mild, practical and environmentally benign method to synthesize mono‐ and bis‐sulfonyl substituted amines. When primary and secondary amines were used in excess, they reacted with N‐sulfonyl aziridines smoothly at room temperature, mainly affording 1:1 ring opening products. Reactions of primary amines with 2 equiv. of aziridines produced 2:1 ring opening products. Some 1:1 products can be cyclized with CS₂ to synthesize N‐sulfonyl cyclothioureas also in water.     

Determination of human muscle protein fractional synthesis rate: an evaluation of different mass spectrometry techniques and considerations for tracer choice

In the present study, different MS methods for the determination of human muscle protein fractional synthesis rate (FSR) using [ring‐¹³C₆]phenylalanine as a tracer were evaluated. Because the turnover rate of human skeletal muscle is slow, only minute quantities of the stable isotopically labeled amino acid will be incorporated within the few hours of a typical laboratory experiment. GC combustion isotope ratio MS (GC‐C‐IRMS) has thus far been considered the ‘gold’ standard for the precise measurements of these low enrichment levels. However, advances in liquid chromatography‐tandem MS (LC‐MS/MS) and GC‐tandem MS (GC‐MS/MS) have made these techniques an option for human muscle FSR measurements. Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino acids derivatized using either N‐acetyl‐n‐propyl, phenylisothiocyanate, or N‐methyl‐N‐(tert‐butyldimethylsilyl)trifluoroacetamide (MTBSTFA) for GC‐C‐IRMS, LC‐MS/MS, and GC‐MS/MS analysis, respectively. A second derivative, heptafluorobutyric acid (HFBA), was also used for GC‐MS/MS analysis as an alternative for MTBSTFA. The machine reproducibility or the coefficients of variation for delta tracer‐tracee‐ratio measurements (delta tracer‐tracee‐ratio values around 0.0002) were 2.6%, 4.1%, and 10.9% for GC‐C‐IRMS, LC‐MS/MS, and GC‐MS/MS (MTBSTFA), respectively. FSR determined with LC‐MS/MS compared well with GC‐C‐IRMS and so did the GC‐MS/MS when using the HFBA derivative (linear fit Y = 1.08 ± 0.10, X + 0.0049 ± 0.0061, r = 0.89 ± 0.01, P < 0.0001). In conclusion, (1) IRMS still offers the most precise measurement of human muscle FSR, (2) LC‐MS/MS comes quite close and is a good alternative when tissue quantities are too small for GC‐C‐IRMS, and (3) If GC‐MS/MS is to be used, then the HFBA derivative should be used instead of MTBSTFA, which gave unacceptably high variability. Copyright © 2014 John Wiley & Sons, Ltd.     

A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald–Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the S_NAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest.     

First total synthesis of prunustatin A

In this study, we achieved the first total synthesis of natural prunustatin A (1), a novel inhibitor of glucose-regulated protein 78 (GRP78) expression. A key feature included a 15-membered ring macrocyclization, which was successfully accomplished by employing Shiina macrolactonization using 2-methyl-6-nitrobenzoic anhydride (MNBA) and 4-dimethylaminopyridine (DMAP).     

Application of oxetane ring opening toward stereoselective synthesis of zincophorin fragment

A stereoselective synthesis of the C1–C11 fragment of zincophorin was achieved by using an intramolecular oxetane ring opening reaction as the key step. The oxetane moiety was synthesized by employing a desymmetrization protocol developed at our group and a non-Evans syn aldol as the key steps toward the synthesis.     

两亲性类树枝状聚合物的合成与药物控释

结合阴离子开环聚合方法合成了内壳为聚（乙氧基乙基缩水甘油醚）,外层为聚环氧乙烷的两亲性类树枝状嵌段共聚物PEEGE-G2-b-PEO（OH）12. 使用核磁共振氢谱以及凝胶渗透色谱等表征了中间产物和目标产物. 选择阿霉素作为实验药物,研究了该聚合物的载药和控释行为. 聚合物的载药率和包覆效率分别为13.07%和45.75%,体外释放试验表现为持续性的释放,并受到释放介质pH影响.