The Total Synthesis of Lasalocid A

A total asymmetric synthesis of the "right half ketone" of the stereo-complex polyether antibiotic, lasalocid A, is described. The [3,3] sigmatropic rearrangements of 0-silylketene acetals derived from esters of 1,4-anhydro-pent-1-enitols (furanoid glycals) and 1,5-anhydro-hex-1-enitols (pyranoid glycals) provided α-substituted-2,5-dihydrofuran-2-acetic acid and α-substituted-5,6-dihydro-2H-pyran-2-acetic acid derivatives. The products are key structural elements which are present in polyether antibiotics. The furanoid and pyranoid glycals were conveniently prepared by reductive fragmentation of 2,3-0-(1-methylethylidene)- furanosyl and pyranosyl chlorides. The synthetic scheme is highly convergent, utilizing a building-block approach with stereo- and regioselective carbon-carbon bond formation between the subunits.