General Approach to the Synthesis of the Chlorosulfolipids Danicalipin A, Mytilipin A, and Malhamensilipin A in Enantioenriched Form

A second-generation synthesis of three structurally related chlorosulfolipids has been developed. Key advances include highly stereocontrolled additions to alpha,beta-dichloroaldehydes, kinetic resolutions of complex chlorinated vinyl epoxide intermediates, and Z-selective alkene cross metatheses of cis-vinyl epoxides. This strategy facilitated the synthesis of enantioenriched danicalipin A, mytilipin A, and malhamensilipin A in nine, eight, and 11 steps, respectively.