Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations
Thesis (Ph.D.)--Memorial University of Newfoundland, 2001. Chemistry Includes bibliographical references Kempane diterpenes such as 1 and 2, which are isolated from the defense secretions of nasute termite soldiers, are attractive and challenging targets for total synthesis. We have developed a high...
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ftmemorialunivdc:oai:collections.mun.ca:theses4/162962 2023-05-15T17:23:34+02:00 Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations Bao, Guanglin, 1965- Memorial University of Newfoundland. Dept. of Chemistry 2000 xviii, 322 leaves : ill. Image/jpeg; Application/pdf http://collections.mun.ca/cdm/ref/collection/theses4/id/162962 Eng eng Electronic Theses and Dissertations (29.45 MB) -- http://collections.mun.ca/PDFs/theses/Bao_Guanglin.pdf a1521863 http://collections.mun.ca/cdm/ref/collection/theses4/id/162962 The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries Diterpenes--Synthesis Ring formation (Chemistry) Text Electronic thesis or dissertation 2000 ftmemorialunivdc 2015-08-06T19:22:43Z Thesis (Ph.D.)--Memorial University of Newfoundland, 2001. Chemistry Includes bibliographical references Kempane diterpenes such as 1 and 2, which are isolated from the defense secretions of nasute termite soldiers, are attractive and challenging targets for total synthesis. We have developed a highly stereoselective route, which is referred to as the Dithiane Route, to the kempane diterpene ring system that possesses all of the required stereogenic centers and sufficient functionality to allow for its conversion to the natural products. Our strategy took advantage of a highly regio- and endo-selective Diels-Alder reaction to construct the benzoindane ring system. 2-[1-[(.e/t-Butyldimethylsilyl)oxy]vinyl]-6,10-dithia-spiro[4,5]-dec-2-ene reacted with 2T6-dimethyl-1,4-benzoquinone to produce a cycloaddition adduct. The diene was prepared through a sequence that involved an alkylation of a dithiane compound with 2-methyl-2-(2-iodoethyl)-1,3-dioxolane. followed by an acid-catalyzed intramolecular aldol condensation. During the course of assembling the seven-membered ring cyclization precursor, a remarkably regioselective acetylide addition to a seemly more hindered carbonyl group was observed. In subsequent steps, a γ-hydroxyl group in an α,β-unsaturated ketone was cleaved by zinc reduction, followed by epimerization of a resulting decalin ring junction and double-bond isomerization catalyzed by ρ-toluene-sulfonic acid. In order to introduce the required double bond in the seven-membered ring at a later stage of the synthesis, a four-carbon side chain required for the target molecule was designed to be installed in two steps. Despite the failures of our "First Route" and "Diether Route", the Dithiane Route proved to be promising enough for construction of the kempane diterpene ring skeleton and elaboration to the natural products. -- To explore the possibility of introducing a methyl group at C-4 of kempane diterpenes, we investigated an electrophilic reaction of a silyl enol ether with 1,3-dithienium tetrafluoroborate and a cyclopropanation of a silyl enol ether. Model studies showed that indirect methylation of the TBS enol ether was successful, but that the subsequent acetylide addition step gave poor regio- and stereoselectivity. -- During the study of a cascade radical cyclization, a 5-exo-d/g, 5-exo-trig tandem process and a 5-exo-dig, 6-exo-trig tandem process were achieved, although in low yield. It had been anticipated that this tandem radical cyclization strategy could provide an efficient approach to polycyclic compounds in high stereoselectivity. Thesis Newfoundland studies University of Newfoundland Memorial University of Newfoundland: Digital Archives Initiative (DAI) Spiro ENVELOPE(-59.000,-59.000,-62.267,-62.267) |
institution |
Open Polar |
collection |
Memorial University of Newfoundland: Digital Archives Initiative (DAI) |
op_collection_id |
ftmemorialunivdc |
language |
English |
topic |
Diterpenes--Synthesis Ring formation (Chemistry) |
spellingShingle |
Diterpenes--Synthesis Ring formation (Chemistry) Bao, Guanglin, 1965- Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations |
topic_facet |
Diterpenes--Synthesis Ring formation (Chemistry) |
description |
Thesis (Ph.D.)--Memorial University of Newfoundland, 2001. Chemistry Includes bibliographical references Kempane diterpenes such as 1 and 2, which are isolated from the defense secretions of nasute termite soldiers, are attractive and challenging targets for total synthesis. We have developed a highly stereoselective route, which is referred to as the Dithiane Route, to the kempane diterpene ring system that possesses all of the required stereogenic centers and sufficient functionality to allow for its conversion to the natural products. Our strategy took advantage of a highly regio- and endo-selective Diels-Alder reaction to construct the benzoindane ring system. 2-[1-[(.e/t-Butyldimethylsilyl)oxy]vinyl]-6,10-dithia-spiro[4,5]-dec-2-ene reacted with 2T6-dimethyl-1,4-benzoquinone to produce a cycloaddition adduct. The diene was prepared through a sequence that involved an alkylation of a dithiane compound with 2-methyl-2-(2-iodoethyl)-1,3-dioxolane. followed by an acid-catalyzed intramolecular aldol condensation. During the course of assembling the seven-membered ring cyclization precursor, a remarkably regioselective acetylide addition to a seemly more hindered carbonyl group was observed. In subsequent steps, a γ-hydroxyl group in an α,β-unsaturated ketone was cleaved by zinc reduction, followed by epimerization of a resulting decalin ring junction and double-bond isomerization catalyzed by ρ-toluene-sulfonic acid. In order to introduce the required double bond in the seven-membered ring at a later stage of the synthesis, a four-carbon side chain required for the target molecule was designed to be installed in two steps. Despite the failures of our "First Route" and "Diether Route", the Dithiane Route proved to be promising enough for construction of the kempane diterpene ring skeleton and elaboration to the natural products. -- To explore the possibility of introducing a methyl group at C-4 of kempane diterpenes, we investigated an electrophilic reaction of a silyl enol ether with 1,3-dithienium tetrafluoroborate and a cyclopropanation of a silyl enol ether. Model studies showed that indirect methylation of the TBS enol ether was successful, but that the subsequent acetylide addition step gave poor regio- and stereoselectivity. -- During the study of a cascade radical cyclization, a 5-exo-d/g, 5-exo-trig tandem process and a 5-exo-dig, 6-exo-trig tandem process were achieved, although in low yield. It had been anticipated that this tandem radical cyclization strategy could provide an efficient approach to polycyclic compounds in high stereoselectivity. |
author2 |
Memorial University of Newfoundland. Dept. of Chemistry |
format |
Thesis |
author |
Bao, Guanglin, 1965- |
author_facet |
Bao, Guanglin, 1965- |
author_sort |
Bao, Guanglin, 1965- |
title |
Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations |
title_short |
Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations |
title_full |
Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations |
title_fullStr |
Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations |
title_full_unstemmed |
Studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations |
title_sort |
studies toward the synthesis of the kempane diterpene ring system, and some cascade radical cyclizations |
publishDate |
2000 |
url |
http://collections.mun.ca/cdm/ref/collection/theses4/id/162962 |
long_lat |
ENVELOPE(-59.000,-59.000,-62.267,-62.267) |
geographic |
Spiro |
geographic_facet |
Spiro |
genre |
Newfoundland studies University of Newfoundland |
genre_facet |
Newfoundland studies University of Newfoundland |
op_source |
Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries |
op_relation |
Electronic Theses and Dissertations (29.45 MB) -- http://collections.mun.ca/PDFs/theses/Bao_Guanglin.pdf a1521863 http://collections.mun.ca/cdm/ref/collection/theses4/id/162962 |
op_rights |
The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. |
_version_ |
1766113342507712512 |