Synthetic studies on pactamycin, a potent antitumor antibiotic

Two synthetic approaches to the functionalized cyclopentane core structure of pactamycin are described. The first approach employed the Pauson-Khand reaction of an enyne prepared from diacetone-D-glucose as a chiral starting material, providing a potentially useful tricyclic intermediate for pactamycin. The second approach involved an intramolecular 1,3-dipolar cycloaddition between the nitrone and acetylene functionalities of a precursor derived from an intermediate of the first approach. The expected isoxazoline cycloadduct was not detected, but instead an aziridine aldehyde was obtained, probably through ring contraction (Baldwin rearrangement) of the expected isoxazoline product. Further transformation provided a highly functionalized cyclopentane bearing an aniline at the C-3 position, but with different stereochemistry from that of pactamycin.