Formal Synthesis of Salinosporamide A

Significance

The key step in the synthesis of the 20S proteasome inhibitor salinosporamde A is a reductive aldol cyclization (C → D) using (Me₃P)₂NiCl₂ as the precatalyst and Et₂Zn as the stoichiometric reductant. The conversion of G into the target required five steps, the last four of which were precedented in the work of Corey (J. Am. Chem. Soc. 2005, 126, 6230) and Pattenden (Org. Biomol. Chem. 2006, 4, 2845).