| Developing a convergent and efficient synthetic route that can be used to synthesize taxol and its analogs is the focus of the studies described in this dissertation. The key strategy lies at the construction of taxane's tetracyclic framework from two simple fragments: an AB-ring ketone, and a CD-ring precursor which has an oxetane ring in position. Incorporation of the oxetane D-ring at an early synthetic stage is for the purpose of achieving a high degree of convergency. The research work is composed of three consecutive phases: the synthesis of optically active CD-ring aldehydes, the coupling of CD-ring aldehydes with AB-ring ketones, and the C-ring closure to complete the tetracyclic system. Synthesis of optically pure CD-ring aldehydes has been achieved via three different routes, each starting from an inexpensive carbohydrate material. These CD-ring aldehydes have been incorporated with the available AB-ring ketones to generate ABD-tricyclic intermediates, upon using a bromomagnesium diisopropylamide mediated aldol condensation. The ABD-tricyclics obtained were further transformed into a triketone compound and a tetracyclic ketal acetate, both of them were key intermediates for the C-ring closure. Various methodologies have been investigated for the C-ring closure operation. Sodium anthracenide mediated reductive elimination and in situ cyclization, starting from the ketal acetate intermediate, has shown promise. |
