Ring-closing metathesis towards a formal synthesis of Taxol

Ojeda Porras, Andrea Carolina (2020) Ring-closing metathesis towards a formal synthesis of Taxol. PhD thesis, University of Glasgow.

Abstract

Taxol is one of the most notorious examples in the use of naturally occurring compounds as the basis of modern medications and has been recognized as one of the best anticancer drugs in the 21st century. Nowadays, Taxol and its derivatives are the largest selling anticancer drugs generating a revenue of more than three billion dollars annually. Due to its structural complexity, Taxol has been one of the main targets for synthetic chemists around the world and several total and formal synthesis have been published. Two different synthetic efforts toward a formal synthesis of Taxol are presented in this thesis.

Initially, a ring-closing dialkene alkyne metathesis (RCDEYM) is studied to form the Taxol skeleton. The primary target is the intermediate described by Holton during his synthesis of Taxol. The formation of the ABC tricyclic core by a cascade RCDEYM reaction constitutes the key step of this approach. On the other hand, the target molecule in the second route is a C7 deoxygenated tricyclic core and a relay ring-closing methatesis (RRCM) was envisioned for the construction of the B ring. Installation of the tether would be possible by a Julia Kocienski olefination.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Taxol, total synthesis, ring-closing metathesis.
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Prunet, Dr Joëlle
• Date of Award: 2020
• Depositing User: Andrea Carolina Ojeda Porras
• Unique ID: glathesis:2020-81743
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 22 Oct 2020 15:05
• Last Modified: 14 Sep 2022 12:54
• Thesis DOI: 10.5525/gla.thesis.81743
• URI: https://theses.gla.ac.uk/id/eprint/81743