Total synthesis of sulfobacin A through dynamic kinetic resolution of a racemic β-keto-α-amino ester hydrochloride

A total synthesis of sulfobacin A, a von Willebrand factor receptor antagonist, is described. Our synthetic approach relies uniquely on catalytic asymmetric reactions for the creation of the three stereogenic centers without using chiral building blocks. The key steps of this short route to sulfobacin A involve ruthenium-mediated asymmetric hydrogenation reactions of a beta-keto ester and a racemic beta-keto-alpha-amino ester hydrochloride to afford, respectively, the corresponding enantiomerically pure beta-hydroxy ester and the enantioenriched anti beta-hydroxy alpha-amino ester hydrochloride through dynamic kinetic resolution. (C) 2004 Elsevier Ltd. All rights reserved.