Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• . Keywords: asymmetric borylation; GAP chemistry; organophosphorous; N-phosphinylimine; Velcade; Introduction The synthesis of chiral α-aminoboronic acids and their derivatives has attracted much attention in the organic and medicinal chemistry communities because of their importance for drug discovery and

• new compounds containing achiral/chiral N-phosphonyl and chiral N-phosphinylimines, and the reactions of these compounds. The requirements of GAP chemistry are shown by the fact that the functional groups of the reactants should generate products of adequate solubility. The GAP products should be

• different conditions. Moreover, the GAP auxiliaries have been proven to be easily deprotected under several conditions for re-use. Herein, we report the synthesis of the anticancer drug Velcade and its derivatives of chiral α-aminoboronic esters via GAP chemistry. Simple operations are needed during