General Approach to the Synthesis of the Chlorosulfolipids

ABSTRACT: A second-generation synthesis of three structur-ally related chlorosulfolipids has been developed. Key advances include highly stereocontrolled additions to α,β-dichloro-aldehydes, 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 malhamen-silipin A in nine, eight, and 11 steps, respectively. ■ INTRODUCTION AND BACKGROUND Almost 40 years after the first report of their existence,1,2 intense activity aimed at the chemical synthesis of the chlorosulfolipids (1−5, Figure 1) began independently and essentially simultaneously in at least four research group