Synthesis of proteasome inhibitor 6-deoxy-omuralide and its enantiomer using stereoselective alkylation of substituted proline ester.

Abstract

A potent 20S proteasome inhibitor, 6-deoxy-omuralide was stereoselectively synthesized in 20 steps with 5.1% overall yield staring from a chiral boron agent and d-glyceraldehyde acetonide. The stereoselective alkylation of the substituted proline ester with 3-iodo-2-methylprop-1-ene served as the key step. The enantiomer of 6-deoxy-omuralide was achieved in 20 steps with 4.6% overall yield by just changing the chiral boron reagents in the first step. Our current work provides a flexible approach to 6-deoxy-omuralide and its enantiomer with the adornment at the C4 position.