A Synthetic Approach to Diverse 3-Acyltetramic Acids via <i>O</i>- to <i>C</i>-Acyl Rearrangement and Application to the Total Synthesis of Penicillenol Series

For the efficient approach to medicinally important α-branched 3-acyltetramic acids, the key reaction of <i>O</i>- to <i>C</i>- acyl rearrangement using α-amino-acid-derived 4-<i>O</i>-acyltetramic acids was extensively examined in the presence of various metal salts. Use of CaCl₂ or NaI dramatically changed the results in the reaction efficiency and rapidly brought about the desired α-branched 3-acyltetramic acids in markedly improved yields. We also discuss an epimerization at C5 stereocenter under the rearrangement conditions as well as the tolerance for structural variation at C3 and C5. In addition to the preceding success in the total synthesis of new cytotoxic tetramic acid, penicillenol A₁, this methodology could be also applied to the first total synthesis of penicillenol A₂

First Total Synthesis of Epicoccarine A via <i>O</i>- to <i>C</i>-Acyl Rearrangement Strategy

The first total synthesis of antibacterial epicoccarine A isolated from a fungus <i>Epicoccum</i> sp. has been accomplished in 10 steps along with synthetic elaboration of its C5-epimer, highlighting the utility of <i>O</i>- to <i>C</i>-acyl rearrangement of a 4-<i>O</i>-acyltetramic acid derivative. Comparison of spectroscopic properties and specific optical rotations of the synthetic samples with those reported for authentic material has clearly indicated the unspecified absolute stereochemistry of this natural product to be 5<i>S</i>