Synthetic studies toward practical total syntheses of taxol and its analogs

The studies in this dissertation were initiated to investigate various synthetic approaches to taxol and its analogs. The objective was to provide practical means for the production of these analogs to be evaluated as antitumor drugs. The synthetic strategy involves dividing the molecular targets into two fragments: the diterpenoid baccatin III fragment and the amido acid fragment. Each fragment would be independently constructed and subsequently combined to produce taxol. Taxol analogs would be produced by combining analogs of the two fragments. The body of this dissertation is divided into two parts. Part I will describe the construction of the diterpenoid fragment and its analogs while Part II will detail the various methods used to construct the amido acid portion and its analogs. In Part I, a [3,3]sigmatropic rearrangement in tandem with an aldol condensation and dehydration was used to convert the readily available (−)-borneol to an intermediate having the patchouline skeleton. The patchouline skeleton was then converted to the baccatin III skeleton using an epoxy-alcohol fragmentation followed by additional transformations. In Part II, readily available glycolic acid was converted to various $b$-lactam equivalents of the amido acid fragments using both a racemic and an asymmetric version of the ester enolate-imine condensation reaction. Additionally, vertebrate liver enzymes were used in the enantioselective production of these $b$-lactams.