A convergent approach to synthesis of bortezomib: the use of TBTU suppresses racemization in the fragment condensation

Bortezomib is a first-in-class therapeutic antineoplastic agent used for treating patients with multiple myeloma and mantle cell lymphoma. In this paper we report an improved method for synthesis of the title compound using a convergent approach. TBTU was found to efficiently suppress racemization in the fragment condensation. In comparison with the original synthesis, the presented one is shorter by two steps, higher in yield, and provides better atom economy. (C) 2009 Elsevier Ltd. All rights reserved.