Synthesis of Cyanuric Chloride based Chiral Reagent for RP-HPLC Enantioseparation of (RS)-Propranolol

In this work, four cyanuric chloride based chiral reagents were prepared via nucleophile substitution of chlorine atom by L-proline derivatives and characterized by UV, FT-IR, HRMS, NMR and elemental analysis. Racemic propranolol was chosen for the chiral recognition study. The prepared chiral reagents were used in the synthesis of diastereomeric derivatives of (RS)-propranolol, under microwave heating conditions. RP-HPLC was used to separate the prepared diastereomeric derivatives. The effect of varying eluting phase concentrations and sample concentrations was optimized. The DFT calculations were performed using Gaussian 09 Rev A.02 to create the lowest energy optimised structures of diastereomeric derivatives. LOD (0.324 ng mL-1), LOQ (0.972 ng mL-1), calibration range (0.02-2.0 mg mL-1), correlation-coefficient (0.999), and recovery were the validation parameters for the present method (99.09 and 99.81 % for inter-day assay and 98.47 and 99.72 % for intra-day assay).

Using Chiral Magnetic Surface Molecularly Imprinted Polymers for Chiral Separation of Ofloxacin

BackgroundOfloxacin is an important drug with anti-bacterial effects, and (–)-ofloxacin has been shown to have better anti-bacterial activity than racemic ofloxacin. But chiral resolution of compounds is a major challenge worldwide. Many methods do not show high specificity to target molecules, causing errors in the separation of these pharmaceutical molecules, thus affecting the purity of drugs.MethodThe paper mainly research on a method for quick resolution of ofloxacin using chiral magnetic surface molecular imprinting polymers (chiral MMIP). Fe3O4 magnetic nanoparticles coated with silica is acted as the substrate. Chiral reagent is N-octyl-D-glucosamine as monomer, with ofloxacin as the template molecules to prepare magnetic surface molecularly imprinted polymer. The chiral polymer can be combined with (+)-ofloxacin, eventually (-)-ofloxacin was isolated. ResultsFinally by using extermal magnetic field and transmission electron microscopy (TEM), the character of magnetic surface molecularly imprinted polymer is tested, and The product was tested by ultraviolet spectrum and optical rotation tests and was confirmed to be (-)-ofloxacin. ConclusionA simple, rapid, and cost-effective method for separating chiral compounds was established.

Synthesis of Solid-phase Supported Chiral Amines and Investigation of Stereoselectivity of Aldol Reactions of Amine-free Tropinone Enolate

Seven selected chiral mono-, di-, and tridentate amines supported on insoluble polymer were effectively prepared from corresponding primary amines or secondary amino alcohols and Merrifield resin. The reaction of the polymer-supported amines with excess n-butyllithium gave the corresponding lithium amide bases, which were tested in the aldol reactions of tropinone with benzaldehyde. The deprotonation reactions were carried out with or without separation of the lithium enolate from polymer-supported reagents. Using the procedure with separation of lithium enolate from supported chiral reagent different results were obtained with or without the addition of LiCl despite the fact that aggregate formation of Merrifield resin supported Li-amides is hindered. Without the additive, the aldol products were obtained in low diastereoselectivity and enantioselectivity, whereas the addition of LiCl resulted in a significant increase of de and ee even when LiCl was added after the deprotonation step and separation of the chiral amine.

Enantiomeric Variability of Distaminolyne A. Refinement of ECD and NMR Methods for Determining Optical Purity of 1-Amino-2-Alkanols

Sample configurations of distaminolyne A (1a); isolated from the ascidians Pseudodistoma opacum and P. cereum, and collected at different sites in New Zealand, were investigated by two methods: Exciton coupled electronic circular dichroism (EC ECD) of the corresponding N,O-dibenzoyl derivative 1b; and chiral reagent derivatization of 1a with (S)- and (R)-α-methoxyphenylacetic acid (MPA), followed by 1H-NMR analysis. Configuration and optical purity of 1a (%ee) was found to vary depending on the geographic distribution of ascidian colonies. An improved method for preparing N,O-diarenoyl derivatives of 1a was optimized. The EC ECD method was found to be complementary to the MPA-NMR method at different ranges of %ee.