Diasteroisomeric Salt Formation and Enzyme-Catalyzed Kinetic Resolution as Complimentary Methods for the Chiral Separation of cis/trans-Enantiomers of 3-Aminocyclohexanol

The paper demonstrates the prep scale synthesis of (1S,3S)-3-aminocyclohexanol via either enzymatic kinetic resolution of Cbz-protected 3-aminocyclohexanols, or via direct diasteroisomeric salt formation with (R)-mandelic acid. The salt formation demonstrates how a single enantiomer, (1S,3S)-3-aminocyclohexanol (R)-mandelate, can be effectively isolated from the cis/trans racemic mixture and subsequently converted to the free amine, (1S,3S)-3-aminocyclohexanol, by ion-exchange chromatography. We have also demonstrated how the other three enantiomers of 3-aminocyclohexanol could be prepared by either diasteroisomeric salt formation or enzymatic kinetic resolution