Serendipitous discovery of a pH-dependant atropisomer bond rotation: toward a write-protectable chiral molecular switch?
J Chromatogr B Analyt Technol Biomed Life Sci
; 875(1): 118-21, 2008 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-18819851
ABSTRACT
Owing to slow rotation of a sterically constrained dimethylamide substituent, two slowly interconverting enantiomers of a preclinical candidate for pharmaceutical development, 1, (6-(3-Chloro-4-fluoro-benzyl)-4-hydroxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-[2,6]naphthyridine-1-carboxylic acid dimethylamide) are observed by chiral chromatography. Isolation of pure enantiomer by preparative chiral chromatography followed by enantiopurity analysis over time allowed for a study of the kinetics of enantiomer interconversion under a variety of conditions. Relatively slow racemization was observed in alcohol solvents, with a half life on the order of 5-10 h. A dramatic influence of aqueous buffer pH on racemization was noted, with higher pH leading to rapid racemization within a few minutes, and lower pH leading to essentially no racemization for periods up to a week. A hypothesis explaining this unusual effect of pH on carboxamide bond rotation is offered, and some suggestions for potential utility of such a system are considered.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Rotação Ocular
/
Cromatografia Líquida de Alta Pressão
/
Dimetilaminas
/
Amidas
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Naftiridinas
Idioma:
En
Revista:
J Chromatogr B Analyt Technol Biomed Life Sci
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos