Synthetic approaches to functionalised piperidines
<p>This thesis is concerned with the synthesis of functionalised piperidines. The piperidine unit is found in numerous alkaloids and other natural products, and has also been incorporated into synthetic compounds of significant therapeutic or strategic synthetic potential. Although numerous s...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
1999
|
| Subjects: |
| _version_ | 1797067312242622464 |
|---|---|
| author | Woods, G Woods, Gordon Alexander |
| author2 | Maloney, M |
| author_facet | Maloney, M Woods, G Woods, Gordon Alexander |
| author_sort | Woods, G |
| collection | OXFORD |
| description | <p>This thesis is concerned with the synthesis of functionalised piperidines. The piperidine unit is found in numerous alkaloids and other natural products, and has also been incorporated into synthetic compounds of significant therapeutic or strategic synthetic potential. Although numerous syntheses of individual piperidine compounds have been published, there are few general routes to this class of compounds, and there is therefore a need for such routes to be developed.</p> <p>Bicyclic lactams derived from (S)-pyroglutamic acid have been shown to be useful synthons in the synthesis of pyrrolidines. An analogous bicyclic lactam was therefore synthesised from (S)-lysine. Alkylations at the carbon atom a- to the lactam carbonyl group were studied in detail. A number of different groups could be introduced in good to excellent yield, and with moderate to good stereoselectivity. The selectivity of these reactions was believed to depend on the shape of the bicyclic system, and a stereoelectronic effect of the nitrogen lone pair.</p> <p>The bicyclic lactam was further elaborated to an activated enone. This was shown to be relatively unreactive to cycloaddition reactions. It is believed that this is because the activating ester group is not conjugated with the carbon-carbon double bond. However, conjugate addition could be achieved in high yield and excellent stereoselectivity using a zinc enolate Reformatsky reagent. An epoxide could also be formed in excellent yield and with excellent stereoselectivity. The Reformatsky adduct was shown to be a suitable substrate for a Pb(IV)-mediated arylation reaction.</p> <p>Examples of the functionalised lactams were deprotected to give hydroxymethyl piperidinones and cyclic amino acids. This route therefore allows access to the desired novel compounds.</p> |
| first_indexed | 2024-03-06T21:54:28Z |
| format | Thesis |
| id | oxford-uuid:4c6fdb6c-c021-447c-8fc9-35241b552850 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:54:28Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:4c6fdb6c-c021-447c-8fc9-35241b5528502022-03-26T15:49:25ZSynthetic approaches to functionalised piperidinesThesishttp://purl.org/coar/resource_type/c_db06uuid:4c6fdb6c-c021-447c-8fc9-35241b552850PiperidineSynthesisLactamsDerivativesEnglishPolonsky Theses Digitisation Project1999Woods, GWoods, Gordon AlexanderMaloney, MMaloney, M<p>This thesis is concerned with the synthesis of functionalised piperidines. The piperidine unit is found in numerous alkaloids and other natural products, and has also been incorporated into synthetic compounds of significant therapeutic or strategic synthetic potential. Although numerous syntheses of individual piperidine compounds have been published, there are few general routes to this class of compounds, and there is therefore a need for such routes to be developed.</p> <p>Bicyclic lactams derived from (S)-pyroglutamic acid have been shown to be useful synthons in the synthesis of pyrrolidines. An analogous bicyclic lactam was therefore synthesised from (S)-lysine. Alkylations at the carbon atom a- to the lactam carbonyl group were studied in detail. A number of different groups could be introduced in good to excellent yield, and with moderate to good stereoselectivity. The selectivity of these reactions was believed to depend on the shape of the bicyclic system, and a stereoelectronic effect of the nitrogen lone pair.</p> <p>The bicyclic lactam was further elaborated to an activated enone. This was shown to be relatively unreactive to cycloaddition reactions. It is believed that this is because the activating ester group is not conjugated with the carbon-carbon double bond. However, conjugate addition could be achieved in high yield and excellent stereoselectivity using a zinc enolate Reformatsky reagent. An epoxide could also be formed in excellent yield and with excellent stereoselectivity. The Reformatsky adduct was shown to be a suitable substrate for a Pb(IV)-mediated arylation reaction.</p> <p>Examples of the functionalised lactams were deprotected to give hydroxymethyl piperidinones and cyclic amino acids. This route therefore allows access to the desired novel compounds.</p> |
| spellingShingle | Piperidine Synthesis Lactams Derivatives Woods, G Woods, Gordon Alexander Synthetic approaches to functionalised piperidines |
| title | Synthetic approaches to functionalised piperidines |
| title_full | Synthetic approaches to functionalised piperidines |
| title_fullStr | Synthetic approaches to functionalised piperidines |
| title_full_unstemmed | Synthetic approaches to functionalised piperidines |
| title_short | Synthetic approaches to functionalised piperidines |
| title_sort | synthetic approaches to functionalised piperidines |
| topic | Piperidine Synthesis Lactams Derivatives |
| work_keys_str_mv | AT woodsg syntheticapproachestofunctionalisedpiperidines AT woodsgordonalexander syntheticapproachestofunctionalisedpiperidines |