Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors

Asymmetric cyclopropanation of styrenes by tert-butyl diazoacetate followed by ester hydrolysis and Curtius rearrangement gave a series of tranylcypromine analogues as single enantiomers. The o - m-and p-bromo analogues were all more active than tranylcypromine in a LSD1 enzyme assay. The m-and p-bromo analogues were micromolar growth inhibitors of the LNCaP prostate cancer cell line as were the corresponding biphenyl analogues prepared from the bromide by Suzuki crosscoupling. (C) 2011 Elsevier Ltd. All rights reserved.