Synthesis of highly substituted heterocycles
<p>This thesis is concerned with studies towards the total synthesis of a class of natural products - the oxazolomycins. Attention was focused on the left-hand side triene fragment and right-hand side lactam heterocyclic system.</p><p>This thesis describes the synthesis of a racemi...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2006
|
| Subjects: |
| _version_ | 1797090584600510464 |
|---|---|
| author | Trippier, P Trippier, Paul Charles |
| author2 | Moloney, M |
| author_facet | Moloney, M Trippier, P Trippier, Paul Charles |
| author_sort | Trippier, P |
| collection | OXFORD |
| description | <p>This thesis is concerned with studies towards the total synthesis of a class of natural products - the oxazolomycins. Attention was focused on the left-hand side triene fragment and right-hand side lactam heterocyclic system.</p><p>This thesis describes the synthesis of a racemic terminal phenyl analogue of oxazolomycin A and C, possessing the left-hand side triene geometry as required. A novel truncated pyridine analogue is also described. The molecules represent a racemic total synthesis of analogues of phthoxazolin A and inthomycins B and C. The synthesis is based upon a crucial Stille cross-coupling reaction between stannane and diene iodide fragments. The stannane fragment was synthesised using literature precedented methods and the vinyl halide prepared using a highly stereoselective Wittig, Takai homologation or Stork reaction leading to a variety of ratios of mixtures of Z, E and E, E diene halides. These investigations led to the availability of 1:1, 3:1 and 1:3 mixtures of Z, Z, E : Z, E, E left hand side triene fragments possessing the required stereochemistries for oxazolomycin A and C.</p><p>Utilising existing methodology developed in the Moloney group, investigations were carried out towards construction of β-keto esters possessing terminal hydroxyl functions, suitable for diastereoselective aldol ring closure. Following extensive protecting group manipulation and N-acylation coupling optimisation, a TIPS protected β-keto acid, existing as predominantly the keto tautomer, was successfully coupled to an oxazolidine heterocycle. This N-acylated oxazolidine upon Dieckmann cyclisation would present an advanced intermediate of opposite configuration (Lserine is used here as a cheaper starting material for the construction of the oxazolidine instead of D-serine) to the oxazolomycin right-hand side.</p> |
| first_indexed | 2024-03-07T03:20:45Z |
| format | Thesis |
| id | oxford-uuid:b758987c-7a0c-4c1b-982c-61b4d383680a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:20:45Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:b758987c-7a0c-4c1b-982c-61b4d383680a2022-03-27T04:47:49ZSynthesis of highly substituted heterocyclesThesishttp://purl.org/coar/resource_type/c_db06uuid:b758987c-7a0c-4c1b-982c-61b4d383680aHeterocyclic compoundsBioactive compoundsEnglishPolonsky Theses Digitisation Project2006Trippier, PTrippier, Paul CharlesMoloney, MMoloney, M<p>This thesis is concerned with studies towards the total synthesis of a class of natural products - the oxazolomycins. Attention was focused on the left-hand side triene fragment and right-hand side lactam heterocyclic system.</p><p>This thesis describes the synthesis of a racemic terminal phenyl analogue of oxazolomycin A and C, possessing the left-hand side triene geometry as required. A novel truncated pyridine analogue is also described. The molecules represent a racemic total synthesis of analogues of phthoxazolin A and inthomycins B and C. The synthesis is based upon a crucial Stille cross-coupling reaction between stannane and diene iodide fragments. The stannane fragment was synthesised using literature precedented methods and the vinyl halide prepared using a highly stereoselective Wittig, Takai homologation or Stork reaction leading to a variety of ratios of mixtures of Z, E and E, E diene halides. These investigations led to the availability of 1:1, 3:1 and 1:3 mixtures of Z, Z, E : Z, E, E left hand side triene fragments possessing the required stereochemistries for oxazolomycin A and C.</p><p>Utilising existing methodology developed in the Moloney group, investigations were carried out towards construction of β-keto esters possessing terminal hydroxyl functions, suitable for diastereoselective aldol ring closure. Following extensive protecting group manipulation and N-acylation coupling optimisation, a TIPS protected β-keto acid, existing as predominantly the keto tautomer, was successfully coupled to an oxazolidine heterocycle. This N-acylated oxazolidine upon Dieckmann cyclisation would present an advanced intermediate of opposite configuration (Lserine is used here as a cheaper starting material for the construction of the oxazolidine instead of D-serine) to the oxazolomycin right-hand side.</p> |
| spellingShingle | Heterocyclic compounds Bioactive compounds Trippier, P Trippier, Paul Charles Synthesis of highly substituted heterocycles |
| title | Synthesis of highly substituted heterocycles |
| title_full | Synthesis of highly substituted heterocycles |
| title_fullStr | Synthesis of highly substituted heterocycles |
| title_full_unstemmed | Synthesis of highly substituted heterocycles |
| title_short | Synthesis of highly substituted heterocycles |
| title_sort | synthesis of highly substituted heterocycles |
| topic | Heterocyclic compounds Bioactive compounds |
| work_keys_str_mv | AT trippierp synthesisofhighlysubstitutedheterocycles AT trippierpaulcharles synthesisofhighlysubstitutedheterocycles |