Type of Document Dissertation Author Koo, Ki Chul Author's Email Address firstname.lastname@example.org URN etd-08222009-032151 Title Studies towards the Total Synthesis of 1-Deoxy-8-demethyl Taxol Degree Doctor of Philosophy Department Chemistry and Biochemistry, Department of Advisory Committee
Advisor Name Title Robert A. Holton Committee Chair Gregory Dudley Committee Member Marie Krafft Committee Member Timothy Logan Committee Member Robert Reeves Outside Committee Member Keywords
- Intermolecular Michael Addition
- Intramolecular Michael Addition
- Total Synthesis
- Lactone Cleavage
- Intramolecular Aldol Reaction
Date of Defense 2009-08-19 Availability unrestricted AbstractThe total synthesis towards 1-deoxytaxol analogs is described. The synthesis relies on new methods to install the C3-C4 bond and to achieve the tricyclic taxane ring skeleton.
The first section describes the formation of the C3-C4 bond via a highly stereoselective one pot tandem enone formation and Michael addition reaction. The precursor for the tandem reaction was prepared from a taxane AB-ring intermediate which was developed for the synthesis of 1-deoxytaxol analogs in our laboratory. An elimination reaction provided a transient á,â-unsaturated ketone and the following intramolecular Michael addition reaction produced the desired C3-C4 bond-linked lactone as a single diastereomer.
Section two describes the highly efficient C-ring closure by consecutive Michael addition and aldol condensation reaction of the previously obtained lactone. Indeed, Michael addition with acrolein led to the corresponding aldehyde adduct. The aldehyde was then employed for the intramolecular aldol condensation reaction to give the crucial tricyclic taxane intermediate.
In the third section, preliminary studies describing the reactivity of the taxane intermediate towards the synthesis of 1,7-dideoxy-8-demethyltaxol are reported.
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