Convergent Total Synthesis of (+)-Mycalamide A

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Abstract
The details of a convergent total synthesis of (+)-mycalamide A are described. Yb(OTf)3−TMSCl-catalyzed cross-aldol reaction conditions are used to synthesize the right segment of mycalamide A. In this reaction, an acid-sensitive aldehyde reacts with methyl trimethylsilyl dimethylketene acetal without epimerization to provide the desired aldol adduct. Additionally, a tetrahydropyran ring, which is the left segment of mycalamide A, is prepared using a novel one-pot δ-lactone formation methodology. Both segments are constructed from a common starting material, d-mannitol. These segments are then coupled in the presence of BuLi, and the functional groups are transformed to complete the synthesis of (+)-mycalamide A.