Title of article :
Serendipitous discovery of a pH-dependant atropisomer bond rotation: Toward a write-protectable chiral molecular switch?
Author/Authors :
Welch، نويسنده , , Christopher J. and Biba، نويسنده , , Mirlinda and Pye، نويسنده , , Philip and Angelaud، نويسنده , , Remy and Egbertson، نويسنده , , Melissa، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
Pages :
4
From page :
118
To page :
121
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.
Keywords :
molecular switch , HPLC-CD , Chiral HPLC , pH-dependant switch , Bond rotation , Atropisomer
Journal title :
Journal of Chromatography B
Serial Year :
2008
Journal title :
Journal of Chromatography B
Record number :
1466460
Link To Document :
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