Synthesis of ABT-341

Significance

ABT-346 inhibits dipeptidyl peptidase IV, a serine protease that deactivates glucose-regulating hormones. It is currently a lead for the treatment of type-2 diabetes. The key step in this remarkably short synthesis of ABT-346 is an asymmetric Michael addition of acetaldehyde to the nitroalkene A catalyzed by the (R)-diphenylprolinol derivative B. Owing to the high efficiency and chemoselectivity of the component reactions, the six-step synthesis could be performed in a single pot in 63% overall yield without isolation of any intermediates.