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Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine
(+)-Tacamonine, a natural product isolated from the Central African plant Tabernaemontana eglandulosa, belongs to the relatively new tacaman class of pentacyclic monoterpenoid indole alkaloids. Its close structural similarity to the potent cerebral vasodilator (-)-vincamone has promoted several effo...
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| Format: | Thesis |
| Language: | English |
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Department of Chemistry
2020
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| _version_ | 1867613150777442304 |
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| access_status_str | Open Access |
| author | Ferreira, Jasmin |
| author2 | Hunter, Roger |
| author_browse | Ferreira, Jasmin Hunter, Roger |
| author_facet | Hunter, Roger Ferreira, Jasmin |
| author_sort | Ferreira, Jasmin |
| collection | Thesis |
| description | (+)-Tacamonine, a natural product isolated from the Central African plant Tabernaemontana eglandulosa, belongs to the relatively new tacaman class of pentacyclic monoterpenoid indole alkaloids. Its close structural similarity to the potent cerebral vasodilator (-)-vincamone has promoted several efforts towards its synthesis, culminating in the appearance of two asymmetric and seven racemic syntheses in the literature. This dissertation details the successful execution of our strategy for the concise, highly-efficient, asymmetric total synthesis of (+)-tacamonine. Chapter 1 serves as an introduction to the tacaman class, including the proposed biosynthesis for members of this class, followed by a review of the reported synthetic approaches to tacamonine. Chapter 2 details the evolution of our approach based on the use of key radical cyclization methodology to ultimately accomplish a total synthesis of the target. An investigation of the diastereoselectivity displayed in the radical cyclization step is also described through computational methods. Our route followed a novel ABC to ABCD to ABCDE ring-construction strategy, which first involved the synthesis of 3,4-dihydro--carboline as well as a chiral acid ester fragment that was acquired through Evans’ auxiliary-controlled alkylation chemistry. The latter set the absolute configuration at C-20 bearing the ethyl group in the D-ring, and thereafter, the two fragments were coupled together before being advanced to the radical cyclization precursor. Radical cyclization then led to the formation of the desired cis D/Ering junction in a diastereomeric ratio of 10:1, the major diastereomer displaying the required C-3/C-14 to C-20 anti-diastereoselectivity. Subsequent global reduction and oxidation/E-ring formation processes afforded the target in 8 steps over 10 operations in 25% overall yield and in 96% enantiomeric excess. X-Ray crystallographic structure determination provided conclusive evidence for the formation of the target. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/31346 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:31:34.243Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| publisher | Department of Chemistry |
| publisherStr | Department of Chemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/31346 Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine Ferreira, Jasmin Hunter, Roger chemistry (+)-Tacamonine, a natural product isolated from the Central African plant Tabernaemontana eglandulosa, belongs to the relatively new tacaman class of pentacyclic monoterpenoid indole alkaloids. Its close structural similarity to the potent cerebral vasodilator (-)-vincamone has promoted several efforts towards its synthesis, culminating in the appearance of two asymmetric and seven racemic syntheses in the literature. This dissertation details the successful execution of our strategy for the concise, highly-efficient, asymmetric total synthesis of (+)-tacamonine. Chapter 1 serves as an introduction to the tacaman class, including the proposed biosynthesis for members of this class, followed by a review of the reported synthetic approaches to tacamonine. Chapter 2 details the evolution of our approach based on the use of key radical cyclization methodology to ultimately accomplish a total synthesis of the target. An investigation of the diastereoselectivity displayed in the radical cyclization step is also described through computational methods. Our route followed a novel ABC to ABCD to ABCDE ring-construction strategy, which first involved the synthesis of 3,4-dihydro--carboline as well as a chiral acid ester fragment that was acquired through Evans’ auxiliary-controlled alkylation chemistry. The latter set the absolute configuration at C-20 bearing the ethyl group in the D-ring, and thereafter, the two fragments were coupled together before being advanced to the radical cyclization precursor. Radical cyclization then led to the formation of the desired cis D/Ering junction in a diastereomeric ratio of 10:1, the major diastereomer displaying the required C-3/C-14 to C-20 anti-diastereoselectivity. Subsequent global reduction and oxidation/E-ring formation processes afforded the target in 8 steps over 10 operations in 25% overall yield and in 96% enantiomeric excess. X-Ray crystallographic structure determination provided conclusive evidence for the formation of the target. 2020-02-26T15:05:08Z 2020-02-26T15:05:08Z 2019 2020-02-26T15:04:58Z Master Thesis Masters MSc http://hdl.handle.net/11427/31346 eng application/pdf Department of Chemistry Faculty of Science |
| spellingShingle | chemistry Ferreira, Jasmin Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine |
| thesis_degree_str | Master's |
| title | Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine |
| title_full | Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine |
| title_fullStr | Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine |
| title_full_unstemmed | Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine |
| title_short | Asymmetric Total Synthesis of the Pentacyclic Indole Alkaloid (+)-Tacamonine |
| title_sort | asymmetric total synthesis of the pentacyclic indole alkaloid tacamonine |
| topic | chemistry |
| url | http://hdl.handle.net/11427/31346 |
| work_keys_str_mv | AT ferreirajasmin asymmetrictotalsynthesisofthepentacyclicindolealkaloidtacamonine |