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

Entry into a new class of potent proteasome inhibitors having high antiproliferative activity by structure-based design.

Proteasome inhibition is a therapeutic concept of current interest in anticancer research. We report here the design, synthesis, and biological characterization of prototypes of a new class of noncovalent proteasome inhibitors showing high activity in biochemical and cellular assays

Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo.

The macrocyclic peptidic BACE-1 inhibitors 2a-c show moderate enzymatic and cellular activity. By exchange of the hydroxyethylene- to ethanolamine-transition state mimetic the peptidic character was reduced, providing the highly potent and selective inhibitor 3. Variation of the P' moiety resulted in the macrocyclic inhibitor 14. Both macrocycles show inhibition of BACE-1 in the brain of APP51/16 transgenic mice, 3 (NB-544) after intravenous and 14 (NB-533) after oral application