The development of one-pot multi-reaction processes for the synthesis of natural products and biologically active compounds

Calder, Ewen D. D. (2015) The development of one-pot multi-reaction processes for the synthesis of natural products and biologically active compounds. PhD thesis, University of Glasgow.

Abstract

This thesis is divided into four chapters in which one-pot processes have been developed and utilised for the synthesis of biologically active compounds. The work in the first chapter outlines the 13-step total synthesis of D -ribo- and L - arabino-phytosphingosine from D -ribose. This process employed a microwave promoted Overman rearrangement of an allylic trichloroacetimidate to install the amine functionality.

In the second and third chapters, the development of a one-pot, two-step Overman/ring closing metathesis process is detailed. The synthesis of three different classes of starting material is also shown. This one-pot process was used as the key step in the synthesis of four oxybenzo[c]phenanthridine natural products and the partial synthesis of an ACAT inhibitor. The potential for further functionalisation of the products by oxidation and reduction was also explored.

In the final chapter, a one-pot allylboration/Heck process for the synthesis of indan-1-ols is described. Optimisation and an investigation of the scope of the process are also presented. The process was then altered to allow the use of a chiral phosphoric acid catalyst for the asymmetric synthesis of these compounds.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Published in part as: E. D. D. Calder, A. M. Zaed and A. Sutherland, Preparation of anti-Vicinal Amino Alcohols: Asymmetric Synthesis of D -erythro-Sphinganine, (+)-Spisulosine, and D - ribo-Phytosphingosine, J. Org. Chem., 2013, 78, 7223. E. D. D. Calder, F. I. McGonagle, A. H. Harkiss, G. A. McGonagle and A. Sutherland, Preparation of Amino-Substituted Indenes and 1,4-Dihydronaphthalenes Using a One-Pot Multireaction Approach: Total Synthesis of Oxybenzo[c]phenanthridine Alkaloids, J. Org. Chem., 2014, 79, 7633. E. D. D. Calder, S. A. I. Sharif, F. I. McGonagle and A. Sutherland, One-Pot Synthesis of 5-Amino-2,5-Dihydro-1-Benzoxepines: Access to Pharmacologically Active Heterocyclic Scaffolds, J. Org. Chem., 2015, 80, 4683. E. D. D. Calder and A. Sutherland, Enantioselective Synthesis of 3-Methylene-indan-1-ols via a One-pot Allylboration-Heck Reaction of 2-Bromobenzaldehydes, Org. Lett., 2015, 17, 2514.
• Keywords: Chemistry, Organic chemistry, Synthesis, Natural product, Overman rearrangement, One-pot multi-reaction processes
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Andrew, Dr. Sutherland
• Date of Award: 2015
• Depositing User: Ewen D D Calder
• Unique ID: glathesis:2015-6667
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 07 Sep 2015 08:42
• Last Modified: 05 Oct 2015 09:40
• URI: https://theses.gla.ac.uk/id/eprint/6667