Methodology for the synthesis of NP25302 and other bioactive natural products
<p>Total synthesis of the pyrrolizidine alkaloid NP25302: (+)-NP25302 is an unusual vinylogous urea containing pyrrolizidine alkaloid shown to exhibit cell adhesion inhibition. It was envisaged that this natural product could be accessed by a novel 5-<em>endo</em>-dig cyclisation t...
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| Format: | Thesis |
| Language: | English |
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2011
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| _version_ | 1797088596373536768 |
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| author | Stevens, K |
| author2 | Robertson, J |
| author_facet | Robertson, J Stevens, K |
| author_sort | Stevens, K |
| collection | OXFORD |
| description | <p>Total synthesis of the pyrrolizidine alkaloid NP25302: (+)-NP25302 is an unusual vinylogous urea containing pyrrolizidine alkaloid shown to exhibit cell adhesion inhibition. It was envisaged that this natural product could be accessed by a novel 5-<em>endo</em>-dig cyclisation to construct the pyrrolizidine core, and a Curtius rearrangement to install the vinylogous urea motif. This methodology was first tested on a model system, furnishing <em>nor</em>-NP25302 from L-proline in 12 steps and 9% overall yield. The total synthesis of (±)-NP25302 was completed in 9 steps and 26% overall yield from ethyl 2-nitropropionate using similar methodology.</p><p>Studies into the stereospecificity of the Au(I)-catalysed cyclisation of monoallylic diols: During the synthesis of (+)-isoaltholactone in the Robertson group, the key Au(I)-catalysed cyclisation was observed to occur with some stereospecificity. Further investigations were therefore conducted into the stereochemical outcome of this reaction using stereodefined allylic alcohols, and from the combined results a mnemonic was proposed to predict the stereochemistry of the products of this reaction.</p><p>Studies into the total synthesis of ascospiroketals A and B: Investigations were conducted into the total synthesis of the recently isolated natural products ascospiroketals A and B. A second generation synthesis was used to construct advanced intermediates 1 and 2.</p> |
| first_indexed | 2024-03-07T02:52:21Z |
| format | Thesis |
| id | oxford-uuid:ae18879e-d75e-4280-ba55-1ae08e64034f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:52:21Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:ae18879e-d75e-4280-ba55-1ae08e64034f2022-03-27T03:40:22ZMethodology for the synthesis of NP25302 and other bioactive natural productsThesishttp://purl.org/coar/resource_type/c_db06uuid:ae18879e-d75e-4280-ba55-1ae08e64034fSynthetic organic chemistryOrganic synthesisEnglishOxford University Research Archive - Valet2011Stevens, KRobertson, J<p>Total synthesis of the pyrrolizidine alkaloid NP25302: (+)-NP25302 is an unusual vinylogous urea containing pyrrolizidine alkaloid shown to exhibit cell adhesion inhibition. It was envisaged that this natural product could be accessed by a novel 5-<em>endo</em>-dig cyclisation to construct the pyrrolizidine core, and a Curtius rearrangement to install the vinylogous urea motif. This methodology was first tested on a model system, furnishing <em>nor</em>-NP25302 from L-proline in 12 steps and 9% overall yield. The total synthesis of (±)-NP25302 was completed in 9 steps and 26% overall yield from ethyl 2-nitropropionate using similar methodology.</p><p>Studies into the stereospecificity of the Au(I)-catalysed cyclisation of monoallylic diols: During the synthesis of (+)-isoaltholactone in the Robertson group, the key Au(I)-catalysed cyclisation was observed to occur with some stereospecificity. Further investigations were therefore conducted into the stereochemical outcome of this reaction using stereodefined allylic alcohols, and from the combined results a mnemonic was proposed to predict the stereochemistry of the products of this reaction.</p><p>Studies into the total synthesis of ascospiroketals A and B: Investigations were conducted into the total synthesis of the recently isolated natural products ascospiroketals A and B. A second generation synthesis was used to construct advanced intermediates 1 and 2.</p> |
| spellingShingle | Synthetic organic chemistry Organic synthesis Stevens, K Methodology for the synthesis of NP25302 and other bioactive natural products |
| title | Methodology for the synthesis of NP25302 and other bioactive natural products |
| title_full | Methodology for the synthesis of NP25302 and other bioactive natural products |
| title_fullStr | Methodology for the synthesis of NP25302 and other bioactive natural products |
| title_full_unstemmed | Methodology for the synthesis of NP25302 and other bioactive natural products |
| title_short | Methodology for the synthesis of NP25302 and other bioactive natural products |
| title_sort | methodology for the synthesis of np25302 and other bioactive natural products |
| topic | Synthetic organic chemistry Organic synthesis |
| work_keys_str_mv | AT stevensk methodologyforthesynthesisofnp25302andotherbioactivenaturalproducts |