Evaluation of the contribution to enantioselectivity of quinine and quinidine scaffolds in chemically and physically mixed chiral selectors

Abstract

Three "dimeric" C(9)-carbamates of quinine (QN) and quinidine (QD), that is, QN-QN, QD-QD, and QN-QD (chemically prepared mixture of the two cinchona-derived subunits), separated by an ethylene spacer were synthesized and used as chiral selectors for HPLC and capillary electrophoresis (CE) for the resolution of chiral acids. The chiral recognition abilities of these dimers and of several physically prepared mixtures thereof were compared in order to estimate the contribution of every cinchona scaffold to the overall enantioselectivity. The diverse phenomena observed in nonaqueous capillary electrophoresis (NACE), either using the selector added to the background electrolyte (BGE) in the total filling or partial filling mode, led us to rationalize, taking into account the relative mobilities of the chiral selectors in the capillary. The chromatographic and electrophoretic properties were compared with those of the corresponding "monomeric" QN and QD carbamates.

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

“…Enantioselectivity was also similar for selectors derived from QN with tert-butyl and adamantyl substituents, but with a carbamate function (7 and 8) [10].…”

“…The chiral stationary phases (CSPs) were prepared as described previously by immobilization of the chiral selectors 1-10 on to 3-mercaptopropyl silanized silica gel then end-capping with 1-hexene [3,7,10]. The exhaustively washed and dried modified silica gels were subjected to elemental analysis, and the selector load- Table I.…”

“…Several types of derivative with diverse functionality and substituents have been prepared and investigated in detail, by use of different separation techniques (HPLC, CE, CEC and SFC) [2 10]. In the current work, the synthesis of a series of new O9-hydrazide QN derivatives (1-6) is presented, together with similarly substituted carbamate derivatives (7)(8)(9)(10), as depicted in Figure 1. After covalent fixation on silica gel the ten novel chiral stationary phases (CSPs) which resulted were chromatographically tested and their enantioselectivity was investigated.…”

“…In this context the naturally occurring alkaloids quinine (QN) and quinidine (QD) have been used by our research group to develop anion-exchange selectors for the resolution of chiral analytes. In recent years several types of cinchona alkaloid derivatives have been prepared and tested as exceptional enantiodiscriminating agents for the resolution of all types of acidic compound [2][3][4][5][6][7][8][9][10]. It is a matter of fact that the analytical and preparative separation of polar or charged molecules is of special significance because amino acids and their derivatives are included in this group and few commercially available CSPs are suitable for their resolution.…”

Enantioseparation of Neutral Compounds on a Quinine Carbamate-Immobilized Zirconia in Reversed-Phase Capillary Electrochromatography

“…[3][4][5][6] CSPs based on the use of carbamoylated derivatives of QN and quinidine as anionexchange type selectors were found to be highly stereoselective for the direct resolution of chiral acids in reversed-phase LC [7][8][9][10][11][12][13][14][15][16][17][18][19][20] and CEC. [21][22][23][24][25][26][27] Chiral recognition mechanism on carbamoyl QNimmobilized stationary phases in organic-aqueous buffer mobile phases involves simultaneously ion pairing, and differential hydrogen bonding (HB), π-π and van der Waals interactions between carbamoyl QN and enantiomers of the chiral analyte.…”