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法尼基蛋白转移酶抑制剂前体α-羟基法尼基膦酸二甲酯对映体的手性液相色谱分离及手性光学性质

Chiral liquid chromatography separation and chiroptical properties of the enantiomers of dimethyl alpha-hydroxyfarnesylphosphonate, a precursor of a farnesyl protein transferase inhibitor.

作者信息

Caccamese Salvatore, Scivoli Giovanna, Du Yanming, Wiemer David F

机构信息

Dipartimento di Scienze Chimiche, Università di Catania, Italy.

出版信息

J Chromatogr A. 2002 Aug 9;966(1-2):221-5. doi: 10.1016/s0021-9673(02)00736-7.

DOI:10.1016/s0021-9673(02)00736-7
PMID:12214697
Abstract

The HPLC enantiomeric separation of racemic and non-racemic samples of dimethyl alpha-hydroxyfarnesylphosphonate (1) was accomplished using Chiralcel OD as chiral stationary phase. Single enantiomers were isolated by semipreparative HPLC and their CD spectra and optical rotations were measured. The method ascertains enantiomeric excess of 1, obtained by oxidation of dimethylfarnesylphosphonate with enantiopure oxaziridines, avoiding converting the enantiomers to diastereomers by the use of a chiral auxiliary. Stability of the solutions of 1 is strongly dependent on the nature of the solvent.

摘要

使用手性固定相Chiralcel OD完成了α-羟基法呢基膦酸二甲酯(1)的外消旋和非外消旋样品的HPLC对映体分离。通过半制备HPLC分离出单一对映体,并测量了它们的圆二色光谱和旋光度。该方法确定了通过用对映体纯的恶唑烷氧化法呢基膦酸二甲酯得到的1的对映体过量,避免了使用手性助剂将对映体转化为非对映体。1溶液的稳定性强烈依赖于溶剂的性质。

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