(116a) Chiral Self Assembled Monolayers as Resolving Auxiliaries in the Crystallization of Valine

Chiral drugs are a subgroup of drug substances that contain one or more chiral centers. For reasons of safety and efficacy, the pure enantiomer is usually preferred over the racemate in many marketed dosage forms. Thus, resolution of racemic mixtures is an active area of research. The most common type of crystalline racemate is that in which the two enantiomers are present in equal quantities in a well-defined arrangement within the crystal lattice. The resultant homogeneous solid phase is called a racemic compound. Racemic compound systems have two eutectic points equidistant from the 50:50 composition point and cannot be resolved into either of the pure enantiomers in a single crystallization operation. In this work, chiral self assembled monolayers (SAMs) on gold were employed as resolving auxiliaries in the crystallization of the amino acid valine which crystallizes as a racemic compound. Results showed the ability to obtain one enantiomer in excess on the crystals grown on the chiral SAMs when starting with racemic solutions. The enantiomer obtained in excess was the one having opposite chirality to the monolayer being used. In addition, it was possible to obtain crystals of the pure enantiomer when starting with a solution having an enantiomeric excess value of 50%. Control experiments carried out without chiral SAMs showed that at equilibrium, mixtures of the pure enantiomer and racemic compound were obtained under these conditions. The enantiomer obtained on the chiral SAMs was the one that was initially present in excess regardless of the chirality of the monolayer being used.