Synthesis of 2'-O-benzoyl-3-keto-6-O-propargyl-11,12-carbamoyl erythromycin A

An efficient and practical synthesis of 2‘-O-benzoyl-3-keto-6-O-propargyl-11,12-carbamoyl erythromycin A (4) is described. The semisynthetic macrolide was prepared on large scale in seven steps in 38% overall isolated yield from the readily available bis(trimethylsilyloxy) ether of erythromycin A oxime ketal (5). The chemistry, which required no chromatography, involved selective hydrolysis, alkylation, and hydroxyl protection transformations.