Recent Patents on the Optical Resolution of Amino Acid Enantiomers by Crystallization from Solution

Adrian   E.   Flood

Abstract

Amino acids are a significant class of compounds in a number of different application areas, including pharmaceuticals, nutrition, and nonlinear optical materials. Nearly all amino acids are chiral molecules, and appear in Dand L-forms (enantiomers) which are mirror images of each other and thus share the same chemical properties (if they do not interact with another chiral molecule), apart from their optical rotation. Although the α-amino acids are ubiquitous in natural materials, industrially it is more convenient to produce them with chemical syntheses, which typically are not specific to a desired enantiomer and therefore produce a racemic mixture having equal quantities of the two enantiomers. In most applications of the materials a pure enantiomeric form is required and thus the racemic mixture must be separated into its component enantiomers, a process which is typically known as optical resolution. Optical resolution is often a difficult process because the components separated have identical properties, however a range of ingenious techniques has been developed to perform the resolution. This article reviews the patented techniques to achieve optical resolution of amino acids using methods involving crystallization from solution. These methods represent the most industrially significant resolution methods, in particular preferential crystallization and crystallization of diastereomer salts. A short summary of several types of techniques not using crystallization is also presented.

Keywords: Amino acid, Optical resolution, Enantiomer, Preferential crystallization, Resolution via diastereomer salts, Dutch resolution, α-amino acid, β-amino acid