Successive β‐Glycosylations of Tiacumicinone: Formal Total Synthesis of Tiacumicin B and Access to a d‐Mannoside Analog

A formal total synthesis of the natural macrolide antibiotic tiacumicin B is described featuring successive and selective glycosylations of tiacumicinone. The challenging β‐facial selectivity of these key glycosylation steps was achieved by using noviosyl or rhamnosyl donors equipped with a phenyl sulfoxide leaving group and a 3‐O‐picoloyl group ensuring an efficient remote stereodirecting effect. Compared with our former total synthesis, this strategy enables us to save steps and gain access to new analogs. This was demonstrated by the replacement of the rhamnosidic moiety by a d‐mannose derivative.