Chiral derivatization reagents for drug enantioseparation by high‐performance liquid chromatography based upon pre‐column derivatization and formation of diastereomers: enantioselectivity and related structure

Structures and related enantioselectivities of the respective chiral derivatization reagents (CDRs) for drug enantioseparation by high‐performance chromatography based upon pre‐column derivatization and diastereomeric formation are reviewed. The elution order of diastereomers caused reaction of some CDRs with enantiomeric amino acids and carboxylic acids. The development of new CDRs available for indirect HPLC methods is also discussed. Copyright © 2001 John Wiley & Sons, Ltd. Abbreviations used: ABD‐APy 4‐(aminosulfonyl)‐7‐(3‐aminopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole Ace‐L‐Cys N‐acetyl‐L‐cysteine Ace‐D‐Pen N‐acetyl‐D‐penicillamine AITC 2,3,4‐tri‐O‐acetyl‐α‐D‐arabinopyranosyl isothiocyanate AEA 1‐(1‐anthryl)ethylamine or 1‐(2‐anthryl)ethylamine APH 2‐amino‐7‐phosphonoheptanoic acid APB 2‐amino‐4‐phosphonobutanoic acid APV 2‐amino‐5‐phosphonvaleric acid APMB 2‐[4‐(1‐aminoethyl)phenyl]‐6‐methoxybenzoxazole Boc‐L‐Cys N‐tert‐butoxycarbonyl‐L‐cysteine Bz‐L‐Cys N‐benzoyl‐L‐cysteine But‐But tert‐butyl 3‐(chloroformoxy)butyrate BZOP‐Cl benoxaprofen chloride BEIT 1‐(2‐naphthyl)ethyl isothiocyanate BGIT 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl isothiocyanate CAZT‐Ala‐NH2 N2‐[2‐(4‐chloro‐6‐(4‐phenylazoanilino)‐1,3,5‐triazinyl)]‐L‐alanine amide 2‐Chl‐L‐ISMN 2‐chlorocarbonyl‐L‐isosorbide 5‐mononitrate 5‐Chl‐L‐ISMN 5‐chlorocarbonyl‐L‐isosorbide 2‐mononitrate 5‐Chl‐L‐IMMN 5‐chlorocarbonyl‐L‐isomannide 2‐mononitrate 5‐Chl‐L‐ISMA 5‐chlorocarbonyl‐L‐isosorbide 2‐monoacetate CMNT‐Ala‐NH2 N2‐[2‐(4‐chloro‐6‐(4‐methoxy‐1‐naphthyl)‐1,3,5‐triazinyl)]‐L‐alanine amide CMOT‐Ala‐NH2 N2‐[2‐(4‐chloro‐6‐methoxy‐1,3,5‐triazinyl)]‐L‐alanine amide CNOT‐Ala‐NH2 N2‐[2‐(4‐chloro‐6‐(2‐naphthoxy)‐1,3,5‐triazinyl)]‐L‐alanine amide DATAAAN (R,R)‐O,O‐diacetyl tartaric acid anhydride DBOSAAN (R,R)‐O,O‐dibenzyl tartaric acid anhydride DBTAAN (R,R)‐O,O‐dibenzoyl tartaric acid anhydride DEOSAAN (R,R)‐O,O‐diethyl tartaric acid anhydride DMTAAN (R,R)‐O,O‐dimethyl tartaric acid anhydride DTTAAN (R,R)‐O,O‐di‐p‐toluoyl tartaric acid anhydride DANE 1‐(4‐dimethylamino‐1‐naphthyl)ethylamine DBD‐Apy 4‐(N,N‐dimethylaminosulfonyl)‐7‐(3‐aminopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole DBD‐CO‐Hz N‐hydra‐zinoformylmethyl‐N‐methylamino‐4,4‐N,N‐dimethylamino sulphonyl‐2,1,3‐benzoxadiazole DBD‐Pz 4‐N,N‐dimethylamino sulphonyl‐7‐piperazino‐2,1,3‐benzoxadiazole DBD‐Pro 4‐(2‐carboxypyrrolidin‐1‐yl)‐7‐(N,N‐dimethylamino‐sulphonyl)‐2,1,3‐benzoxadiazole DBD‐N‐Me‐Ala 4‐(N‐1‐carboxyethyl‐N‐methyl)amino‐7‐N,N‐dimethylamino‐2,1,3‐benzoxadiazole DBD‐Pro‐COCl 4‐(N,N‐dimethyl aminosulfonyl)‐7‐(2‐chloroformylpyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole DBD‐PyNCS 4‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐7‐(N,N‐dimethylaminosulfonyl)‐2,1,3‐benzoxadiazole ECF 1‐(cyclohexyl)ethyl chloroformate Eth‐But ethyl 3‐(chloroformoxy)butyrate FLEC (+)‐1‐(9‐fluorenyl)ethyl chloroformate FLOP‐Cl flunoxaprofen chloride FDNP‐Ala‐NH2 N2‐(5‐fluoro‐2,4‐dinitrophenyl)‐L‐alanine amide FDNP‐Phe‐NH2 N2‐(5‐fluoro‐2,4‐dinitrophenyl)‐L‐phenylalanine amide FDNP‐Pro‐NH2 N2‐(5‐fluoro‐2,4‐dinitrophenyl)‐L‐proline amide FAZT‐Ala‐NH2 N2‐[2‐(4‐fluoro‐6‐(4‐phenylazoanilino)‐1,3,5‐triazinyl)]‐L‐alanine amide FMOC‐L‐Pro 9‐fluorenylmethyl chloroformate‐L‐proline FMOC‐L‐Phe 9‐fluorenylmethyl chloroformate‐L‐phenylalanine FLOPIC flunoxaprofen isocyanate FDNP‐Val‐NH2 N2‐(5‐fluoro‐2,4‐dinitrophenyl)‐L‐valine amide