Synthesis and incorporation into the brain of di-4-amino-3(RS)-hydroxybutanoic acid maleate

Resolution of 4-amino-3-hydroxybutanamide and 4-amino-3-hydroxybutananilide was carried out with optically active camphor-l0-sulfonic acid and tartaric acid, respectively. Hydrolysis of optically active 4-amino-3-hydroxybutanamide and 4-amino-3-hydroxybutananilide on a strongly acidic resin yielded 4-amino-3(R)-hydroxybutanoic acid (R-GABOB) and 4-amino-3(S)-hydroxybutanoic acid (S-GABOB). As Infrared absorption spectrums of R-GABOB and 4-amino-3(RS)-hydroxybutanoic acid (RS-GABOB) were different, RS-GABOB was shown to be a racemic compound. Although direct resolution of a racemic compound is impossible, RS-GABOB was converted into a racemic mixture as the corresponding salt of mxylenesulfonic acid, and resolution was accomplished by selective crystallization. RS-GABOB is a racemic compound, its incorporation into the brain is a little. It is known that incorpration into the brain of optically active R-GABOB is greater than that of RS-GABOB or optically active S-GABOB. We discovered that the incorporation into the brain of di-RS-GABOB-maleate-1-(14)C, upon i.p. injection was greater than that of RS-GABOB-1-(14)C. As di-RS-GABOB-maleate has the monomolecular action of RS-GABOB in circulative blood, it passes easily through the blood brain barrier.