When performing a chiral resolution at-scale it is important whether the resolving agent can be re-isolated, crystallized to a consistent purity, and thus practically reused. When the resolving agent is a carboxylic acid, this is simpler when the carboxylate salt of an alkali or alkaline earth metal is soluble in water while the free acid precipitates from water. Two common chiral acids have this characteristic: lasalocid and (-)DAG.
Lasalocid
Lasalocid sodium is a veterinary pharmaceutical available in large quantities. It is a chiral carboxylic acid that can be used to form diastereomeric salts with racemic amines. Based on tested examples it is predicted to work most dependably for primary amines that have their chiral center at the alpha or beta position as well as tertiary amines with a proximate chiral center with respect to the nitrogen atom. The ligand is capable of multipoint binding with the amine as it forms hydrogen bonds to many different oxygens. The ligand contains many different chiral centers. The molecule is made by fermentation. The acid is relatively inexpensive. It was covered by US 4,129,580 which expired in 1998.
(-)-2,3;4,6-di-O-isopropylidene-2-keto-L-gulonic acid hydrate also called (-)-DAG
(-)-DAG is also a water-insoluble chiral organic acid that can be used to resolve chiral asymmetric amines.
It is a relatively inexpensive compound that is used an intermediate in the synthesis of Vitamin C. It was first prepared by Reichstein et al. Helv. 17, 311 (1934). Its use for resolution was taught in the expired US patent 3,682,925 (1972).
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