Chiral separation of beta-blockers after derivatization with (-)-alphamethoxy-alpha-(trifluoromethyl)phenylacetyl chloride by gas chromatography.
Gas chromatographic method was investigated for the chiral separation of several beta-blockers(atenolol, betaxolol, bisoprolol, metoprolol and pindolol) using (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent for amino group. Prior to N-acylation, hydroxyl group was converted into O-silyl ethers by react with N-methyl-N-(trimethylsilyl)trifluoroacetamide. The reaction was selective and rapid and the diastereomeric derivatives were well separated by capillary gas chromatography. (R)-isomers were eluted faster than (S)-isomers when (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride was used as the chiral derivatizing agent. But in the opposite sequence when (+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride was used. No racemization was found during the reaction.
Kim
K H
KH
College of Pharmacy, Kangwon National University, Chunchon 200-701, Korea. kyeong@kangwon.ac.kr
Lee
J H
JH
Ko
M Y
MY
Hong
S P
SP
Youm
J R
JR
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000302:isolation & purification*; D002849:Chromatography, Gas; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D007202:Indicators and Reagents; D010648:Phenylacetates; C101363:alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride