This thesis describes work focused on the chemical synthesis and herbicidal activity of the natural product phyllostictine A, a molecule of unique structure and unknown mode of action. Chapter 1 serves to introduce the natural product and describe the known activity of the natural product. Furthermore, it discusses literature methods for the construction of a-methylene-b-lactams, a key component of phyllostictine A. Chapter 2 describes work towards the construction of the macrocyclic rings found in phyllostictine A. As a result a-methylene-b-lactams have been shown, for the first time, to participate in RCM reactions. Formation of 11- and 12-membered trisubstituted membered rings was possible, however, the nature of the nitrogen substituent has a large impact. For example, 12-membered rings 124, 130 were formed in 37% yield when a para-methoxyphenyl group was utilised, while simple ethyl substitution could only achieve yields of 20%. Boc protected lactam 169 produced only linear dimer 170. The synthesis of tetrasubstituted alkenes via RCM was attempted with lactam 145, however, resulted in an unexpected rearrangement product. Not only was the RCM sensitive to the nitrogen substituent but also the size of ring being formed. For example, 11-membered rings produced significant amounts of the 22-membered dimers 89 and 87. Throughout the RCM reactions performed in this thesis held a preference for the Z-alkene. The trend was confirmed both by NMR shift analysis and X-ray crystallography. Chapter 3 describes work towards the synthesis of 4,4-disubstituted a-methylene-b-lactam subunit of phyllostictine A. Three methods: epoxide rearrangement, carbonylation of methyleneaziridines and carbonylation of 2-bromo-allyl-propenes were explored. Chapter 4 describes the herbicidal activity of phyllostictine A against the single celled algae C. reinhardtii. ED50 data was obtained for phyllostictine A against C. reinhardtii for the first time. Furthermore, it was shown to be comparable to the commercial herbicide glyphosate. Six novel a-methylene-b-lactams synthesised in Chapter 2 were tested for herbicidal activity against C. reinhardtii which has enabled us to develop preliminary structure-activity relationships.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:644921 |
| Date | January 2014 |
| Creators | Coe, Samuel |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/67101/ |
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