The Synthesis of Oxazole-containing Natural Products

The first section describes the synthesis of the C1' to C11' side chain of leucascandrolide A. The key step of the synthesis is a modified Robinson-Gabriel synthesis of the oxazole. The C1' to C11' side chain was constructed in 9 steps and 7% overall yield.The second section describes the synthesis of 2-alkynyl oxazoles and subsequent transformations into a variety of useful motifs. The conjugate addition of nucleophiles to 2-alkynyl oxazoles under basic conditions affords vinyl ethers, vinyl thioethers and enamines. The addition of ethanedithiol affords dithiolanes that can be transformed into ethyl thioesters and ketones. Nucleophilic additions of thiols to 2-alkynyl oxazolines affords oxazoline thioethers. Additions of halides under acidic conditions stereoselectively affords vinyl halides that can be further transformed by Sonogashira cross-coupling reactions.The third section describes the synthesis of (-)-disorazole C1 and analogs. The macrocycle was constructed with minimal protecting group manipulations, using mild esterification and Sonogashira cross-coupling reactions. The convergent synthesis of disorazole C1 allowed for the synthesis of additional analogs. These analogs include the C14-t-butyl and C17-18-cyclopropane derivatives. Results from preliminary biological evaluations of synthetic intermediates, analogs and derivatives are also discussed