Acetomycin

Baeyer-Villiger oxidation has been used to selectively oxidize one of two methyl ketones (to esters) in the final step of a stereoselective synthesis of (—)-acetomycin, an antibiotic with potential anti-leukemia activity (equation 25)135. This reaction was accomplished using MCPBA as oxidant, with an excess of sodium bicarbonate and 5-/er/-bulyl-4-hydroxy-2-melhyl phenyl sulfide as a radical inhibitor. 

Ozonolysis also plays a key role in the stereoselective synthesis of acetomycin antibiotics. The densely functionalized acetomycin 75 has other stereochemical arrangements 76-78 of interest.72... 

The unselective 6jt-electrocyclization can be avoided with substrates that lack a [3-olefin substituent (Scheme 7.41).116 When chiral, nonracemic versions of these substrates are employed, Woerpel and Calad demonstrated that the cascade reaction efficiently transfers the chiral information. While silver salts were competent catalysts for the diastereoselective formation of silalactone 144 from 1301, on scale-up, copper(II) triflate proved to be more efficient. The authors attribute the poorer performance by silver to product inhibition. In eight steps, silalactone 144 was transformed into the antibiotic (+ Hyu-acetomycin, to further highlight the synthetic utility of the cascade process. 

Tadano, K, Ishihara, J, Ogawa, S, Total synthesis of (—)-acetomycin. Tetrahedron Lett., 31, 2609-2612, 1990. 

In the laboratory of A.M. Echavarren, the total synthesis of the antibiotic (+)-4-ep/-acetomycin was completed by using the stereoselective ester enolate Carroll rearrangement of ( )-butenyl-2-methylacetoacetate as the key step, followed by ozonolysis and acetylation. The stereochemistry of the major isomer resulted from the rearrangement of the ( )-enolate through a chair-like transition state. ... 

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