RESUMO
A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.
RESUMO
Green (reagents and organic solvents saving) analytical chemistry is a new strategy for pharmaceutical analysis. The principles of this idea include primary elimination or at least reduction of the amounts of organic reagents and solvents. In this study, we have provided two simple methods for the analysis of clinical drugs in human plasma. One is the capillary LC (Cap LC) connected to MS-MS, the other is the matrix-assisted laser desorption ionization (MALDI) connected to TOF MS. Sulfonylurea drugs are usually used in diabetes mellitus patients. Diabetes is a syndrome of disordered metabolism resulting in abnormally high blood sugar levels (hyperglycemia). These microscale methods were successfully applied for the monitoring of drug levels in human plasma using gliclazide (a second-generation sulfonylurea) as the test platform. The sensitivity of these methods is sufficient for detecting the gliclazide within a therapeutic range. All the analytical procedures (including human plasma, sample preparation, and flow rate of the analytical system) were at microscale level. These two methods would lower the consumption of organic solvents further safeguarding our environment.