Chiral derivatization reagents for drug enantioseparation by high‐performance liquid chromatography based upon pre‐column derivatization and formation of diastereomers: enantioselectivity and related structure
Authors: Sun Xian Xiang , Sun Ling Zhi , Aboul‐Enein Hassan Y. 
Published: August 2002

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

GITC

2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl isothiocyanate

i‐But‐L‐Cys

N‐isobutanoyl‐L‐cysteine

i‐Val‐L‐Cys

N‐isovaleroyl‐L‐cysteine

LA

leucinamide

methy‐BNCC

2′‐methyl‐1,1′‐binaphthalene‐2‐carbonyl cyanide

MCF

(−)‐methyl chloroformate

Me‐But

methyl 3‐(chloroformoxy) butyrate

MDL

methylated N ϵ ‐dansyl‐L‐lysine

MDNE‐OTf

1‐methyl‐2‐(6,7‐dimethoxy‐2,3‐naphthalimido)ethyl trifluoromethane sulfonate

methoxy‐BNCC

2′‐methoxy‐1,1′‐binaphthalene‐2‐carbonyl cyanide

MeDAP

2‐amino‐ ω ‐ phosphonoalkanoic acid

MNE‐OTf

1‐methyl‐2‐(2,3‐naphthalimido)ethyl trifluoromethane sulfonate

n‐But‐L‐Cys

N‐butanoyl‐L‐cysteine

NBD‐Pro

4‐(2‐carboxypyrrolidin‐1‐yl)‐7‐nitro‐2,1,3‐benzoxadiazole

N‐AA

N‐[2‐(chloroformoxy)propyl]acetamide

NBD‐N‐Me‐Ala

4‐(N‐1‐carboxyethyl‐N‐methyl)‐amino‐7‐nitro‐2,1,3‐benzoxadiazole

NBD‐Pro‐COCl

4‐(2‐chloroformylpyrrolidin‐1‐nyl)‐7‐nitro‐2,1,3‐benzoxadiazole

NAP‐IC

1‐(6‐methoxy‐2‐naphthyl)ethyl isocyanate

NAP‐IT

1‐(6‐methoxy‐2‐naphthyl)ethyl isothiocyanate

NEIT

1‐(1‐naphthyl)ethyl isothiocyanate

NEIC

1‐(1‐naphthyl)ethyl isocyanate

NBD‐PyNCS

4‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐7‐nitro‐2,1,3‐benzoxadiazole

NEA

1‐(1‐naphthyl)ethylamine

NBD‐APy

4‐nitro‐7‐(3‐aminopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole

NPSP‐Cl

4‐nitrophenylsulfonyl‐(s)‐prolyl chloride

β‐ODAP

ω‐N‐oxalyl derivative of L‐α, β‐diaminopropanoic acid

γ‐ODAB

ω‐N‐oxalyl derivative of L‐α, γ‐diminobutanoic acid

δ‐OORN

ω‐N‐oxalyl derivative of orinithine

ϵ‐OLYS

ω‐N‐oxalyl derivative of lysine

PEA

1‐phenylethylamine

PEIC

1‐phenylethyl isocyanate

PEIT

1‐phenylethyl isothiocyanate

PAA

phenyl alanine amide

PAME

phenyl alanine methyl ester

PGIT

2,3,4,6‐tetra‐O‐pivaloyl‐β‐D‐galactopyranosyl isothiocyanate

Pro‐L‐Cys

N‐propanoyl‐L‐cysteine

Tma‐L‐Cys

N‐trimethylacetyl‐L‐cysteine

TFCF

tetrahydro‐3‐furanyl chloroformate

Val‐L‐Cys

N‐valeroyl‐L‐cysteine