New tandem reactions for the synthesis of nitrogen containing natural products

Zaed, Ahmed Mohamed Faraj (2012) New tandem reactions for the synthesis of nitrogen containing natural products. PhD thesis, University of Glasgow.

Abstract

Abstract

During the course of the studies outlined in this thesis, a new approach for the synthesis of the tropane alkaloid, (±)-physoperuvine has been developed using a highly efficient one-pot tandem process which involved the Overman rearrangement and a ring closing metathesis reaction. An asymmetric one-pot tandem process has also been employed for the synthesis of the natural product, (+)-physoperuvine. This methodology was also applied to the generation of a late-stage intermediate that could be used in the synthesis of carbocyclic nucleosides, such as noraristeromycin.

In the second part of this thesis, an ether-directed Pd(II)-catalysed Overman rearrangement which had previously been developed by the Sutherland group was applied in conjunction with a cross-metathesis reaction for the stereoselective synthesis of the guanidine alkaloid, (+)-monanchorin in a fourteen-step synthesis.

Further employment of this process provided the first synthesis of clavaminol A, C and H from (R)-glycidol in a rapid and efficient manner. In a similar fashion, (2S,3R)-enantiomers were also synthesised from (S)-glycidol. In addition to this, using similar chemistry, an intermediate protected enone was prepared using a cross-metathesis reaction as the second key step in an approach towards the synthesis of an NO-inhibitor.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Tandem Process: Ring Closing Metathesis Reaction Overman Rearrangement MOM-ether directed overman rearrangement
• Subjects: Q Science > QD Chemistry; R Medicine > RM Therapeutics. Pharmacology; R Medicine > RS Pharmacy and materia medica
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Sutherland, Dr. Andrew
• Date of Award: 2012
• Depositing User: Mr Ahmed Mohamed Faraj Zaed
• Unique ID: glathesis:2012-3927
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 20 Feb 2013 09:27
• Last Modified: 20 Feb 2013 13:11
• URI: https://theses.gla.ac.uk/id/eprint/3927