P-24 Log Dを利用した改良Marfey法による絶対立体配置決定(ポスター発表の部)

抄録

The advanced Marfey's method has been developed to nonempirically determine the absolute configuration of primary amine including amino acids and secondary alcohols using liquid chromatography/mass spectrometry (LC/MS) under the reversed phase conditions. In this method, the resolution between the diastereomers derivatized with 1-fluoro-2,4-dinitrophenyl-5-L-leucinamide (L-FDLA) and 1-fluoro-2,4-dinitrophenyl-5-D-leucinamide (D-FDLA) is reflected by the difference of hydrophobicity of the two functional groups at the asymmetric carbon.. However, no effective method has been developed for the estimation of hydrophobicity so far. For this purpose, we introduced log D and applied it to relatively simple primary amines, amino acids and secondary alcohols in the present study. It was found that the difference of the retention times correlated with that of log D for both diastereomers based on experimental results obtained in this study. Furthermore, the method was successfully applied to penicillide. From these results the following procedure is proposed for the non-empirical determination of the absolute configuration of primary amine including amino acids and secondary alcohols: 1) estimate the hydrophobicity by the calculation of log D for two substituent groups at the asymmetric carbon. 2) locate the trans-type arrangement of the two more hydrophobic substituents in the L-DLA derivative and judge the asymmetric carbon to be R or S in the trans-type that is eluted first. 3) derivatize a desired compound with L- or D-FDLA and analyze by LC/MS. 4) compare the elution order with the prospective one and determine the absolute configuration of the asymmetric carbon. The developed method is being applied to more complicated compounds.