OPTICAL RESOLUTION OF ISOCOUMARIN DERIVATIVE

摘要

PROBLEM TO BE SOLVED: To obtain a low-toxic optically active isocoumarin derivative having immunomodulatory activity and neovascularization inhibitory activity by reaction of the racemic modification of an isocoumarin derivative with an optically active phenylethylamine. SOLUTION: The optical resolution of an isocoumarin derivative comprises the following steps: the racemic modification of an isocoumarin derivative of the formula is reacted with an optically active 1-phenylethylamine in an organic solvent (e.g. dioxane) to form and crystallize the diastereomer salt of one of the optically active modifications of the isocoumarin derivative of the formula and the optically active 1-phenylethylamine; and the diastereomer is then fractionally collected and subsequently decomposed with an acid (e.g. hydrochloric acid) or a base to obtain the objective optically active isocoumarin derivative, wherein, in the isocoumarin derivative of the formula where R is methyl group, to obtain the S-modification (+), 1-phenylethylamine of R- modification (+) is pref. used at 0.3-0.6 molar time the isocoumarin derivative, and the operation is conducted pref. at room temperature (15-25 deg.C) for about 1-3 h under agitation.