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

For the efficient approach to medicinally important alpha-branched 3-acyltetramic acids, the key reaction of O- to C- acyl rearrangement using alpha-amino-acid-derived 4-O-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 alpha-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 CS. In addition to the preceding success in the total synthesis of new cytotoxic tetramic acid, penicillenol A(1), this methodology could be also applied to the first total synthesis of penicillenol A(2).