Optically Active γ‐Hydroxy Sulfone Julia Reagents for the Synthesis of Peptidyl Olefin Peptidomimetics

Peptidyl olefin peptidomimetics serve as biologically active compounds or as intermediates for other peptidyl isosteres. We developed a chemoenzymatic stereoselective approach to optically active γ-hydroxy sulfones to be assembled into peptidyl olefins by the Julia reaction. Key enzymatic hydrolysis of prochiral diesters to the corresponding hydroxy esters introduces optical activity. The sequence of the subsequent chemical reactions, either protection–hydrolysis–functionalization or functionalization–hydrolysis–protection, determines the absolute stereochemistry of the final sulfone building block.