Studies in natural product synthesis: Aeruginosin 298-A and diazonamide A

An efficient synthesis of the hydroindole core of aeruginosin 298-A from inexpensive tyrosine was developed and used for a total synthesis of this peptide-like thrombin inhibitor. After comparison of the spectroscopic data for the synthetic and the natural products, the stereochemistry of the leucine fragment was revised to the D-form.; A novel Chan-type rearrangement of imides to α-aminoketones was developed for a planned synthesis of the antitumor agent diazonamide A. The rearrangement was shown to be useful for iterative polyoxazole synthesis and has been successful for acyclic models, including the preparation of the indolyl bisoxazole fragment of diazonamide A. Preliminary work with cyclic systems indicates that more research is necessary for an application to the natural product.; The cationic vinylzirconocene addition to epoxy esters giving vinyl acetals has been extended to a versatile synthesis of substituted 1,4-dicarbonyl compounds and pyridazinones. Divinyl acetals were elaborated using a series of copper-mediated Michael additions and enolate alkylations. This strategy was extended to a fluorous version suitable for combinatorial chemistry wherein purification is achieved by a fluorous liquid-liquid extraction.