Novel cinchona alkaloid O9-hydrazide derivatives as chiral anion-exchange-type selectors: Synthesis and chromatographic evaluation

Abstract

SummarySix new quinine (QN) O9-hydrazide derivatives with different substituents have been synthesized and immobilized on porous silica gel for HPLC. The chiral resolving power of these anion-exchange-type chiral stationary phases (CSPs) has been investigated and compared with that of four carbamate QN derivatives with analogous substitution. The unsubstituted QN-hydrazide derivative was usually the best chiral selector of the hydrazide series. Among the substituted hydrazide derivatives the introduction of a tritylcarbonyl or a tertbutylcarbonyl group at the fl position of the hydrazide function improved chiral recognition by the resulting CSPs. Although carbamate functionality seemed to favour the resolution of the enantiomers of many of the racemic compounds tested, the hydrazide series resulted in better separations of the enantiomers of the DNP derivatives of amino acids and of certain acidic drugs of therapeutic interest, such as the profens. The selectivity factors of these types of compounds on these QN-hydrazide derivatives are the best yet obtained on QNderived chiral selectors.

Resolution of Racemates and Enantioselective Analytics by Cinchona Alkaloids and Their Derivatives

“…In contrast to the N-monosubstituted (-NHR) carbamates, their N-methylated (-NMeR) counterparts exhibit very poor performance [60]. Similarly, the replacement of the carbamoyl group with N-substituted hydrazide resulted in a significant drop of chiral discrimination toward typical analytes [101] but resulted in a better separations of the DNP-derivatized amino acids and certain acidic drugs, such as the profens. iii.…”

Measurement of Solution-Phase Chiral Molecular Recognition in the Gas Phase Using Electrospray Ionization-Mass Spectrometry

“…More than 10 years focused on cinchona alkaloid-derived systems has indeed led to development of diverse, efficient, and useful chiral selector system for acidic analytes, in particular, and a wealth of information concerning stereoselective molecular recognition in solution-phase separations, in general. ,,,− In retrospect, the evolution of the cinchona alkaloid selector molecules and, for that matter, any selector designed to interact with an analyte of interest in a high affinity and selective fashion could have been achieved much more quickly. The main drawback of evaluating new selector molecules via measurement of chromatographic selectivity factors (α) is the need to synthesize at least 50 mg or greater quantities of an SO compound to be immobilized onto an appropriate support material.…”

Enantiomer Separation by Countercurrent Chromatography Using Cinchona Alkaloid Derivatives as Chiral Selectors

“…Exhaustive investigations have been performed in order to understand the influence of every substituent and functionality to enhance the chiral recognition abilities of this type of selectors 8,[15][16][17] (See general structure in Figure 1.). On one hand, the possibility of protonating the quinuclidine nitrogen of their molecule makes them especially suitable for the resolution of acidic compounds, such as amino acid derivatives and other chiral acidic substances due to ion pair formation.…”