Enaminone-based approaches to the synthesis of alkaloids possessing the pyrrolo[1,2-a]azepine core

Simple item page
dc.contributor.authorMthembu, Siyanda Thabani
dc.date.accessioned2018-11-16T11:40:14Z
dc.date.available2018-11-16T11:40:14Z
dc.date.issued2018
dc.descriptionA thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg. In fulfilment of the requirements for the Degree of Doctor of Philosophy February 2018.en_ZA
dc.description.abstractThis thesis illustrate strides taken toward the construction of the pyrrolo[1,2-a]azepine 4 nucleus via enaminone chemistry developed in this University for creating pyrrolizidine 1, indolizidine 2 and quinolizidine 3 alkaloids. The pyrrolo[1,2-a]azepine 4 core is a fused pyrrolidine and azepine system found in lehmizidine, Stemona, Cephalotaxus alkaloids and other alkaloids. A concise background is given on the nature of enaminones, how they are accessed with strong emphasis on the Eschenmoser sulphide contraction reaction and their versatile reactivity, followed by literature review of this University background on synthesis of alkaloids containing 1, 2 and 3 nuclei. The aims and strategies presented are preceded by literature review of lehmizidine, Stemona, Cephalotaxus alkaloids and some reported synthesis. A range of attempts and successes are reported in chapter 2 for making four-carbon chain length enaminones (via N-alkylation, condensation, thionation, Eschenmoser sulphide contraction and tandem acylation/Michael addition reactions) crucial in creating azepane onto pyrrolidine in an acylation or alkylation ring closing steps yielding lehmizidine like compounds (E)-ethyl 8-oxo- 2,3,5,6,7,8-hexahydro-1H-pyrrolo[1,2-a]azepine-9-carboxylate 144 and (E)-ethyl 2,3,5,6,7,8- hexahydro-1H-pyrrolo[1,2-a]azepine-9-carboxylate 147. Vice versa, the synthesis of two carbon chain length N-alkyl vinylogous amides is demonstrated leading to the formation of pyrroles, ethyl 2-phenyl-6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-3-carboxylate 222, ethyl 2-(4-nitrophenyl)- 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-3-carboxylate 223 and ethyl 2-(4-methoxyphenyl)- 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-3-carboxylate 224 in Knoevenagel condensation reactions similar to those described by Garreth Morgans and Stefania Scalzullo in their PhD theses. The synthesis of 1-benzoyl-6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-2,3-dione 233 and 1-(4-methoxybenzoyl)-6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-2,3-dione 235 in a double acylation reaction between NH vinylogous amides and oxalyl chloride is also demonstrated. In chapter 3, the synthesis of vinylogous urethanes for making the Cephalotaxus core via Nalkylation, condensation, thionation, Eschenmoser sulphide contraction and tandem acylation/Michael addition reactions are described. A variety of attempts of the arylation reaction on vinylogous urethanes are demonstrated leading to a comparison study to ascertain carbon chain length dependency of the step. The synthesis of pyrido[1,2-a]azonine nucleus of Sessilifoliamide alkaloids, which are a subset of the Stemona alkaloids demonstrated in chapter 4 is in line with our fascination with bigger ringed alkaloids. The synthetic route is presented leading the formation of compounds 1-benzoyl-3- methyl-2,3,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-4(6H)-one 337, 3-methyl-1-(4- nitrobenzoyl)-2,3,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-4(6H)-one 338 and 1-(4- methoxybenzoyl)-3-methyl-2,3,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-4(6H)-one 339.en_ZA
dc.description.librarianLG2018en_ZA
dc.format.extentOnline resource (ix, 267 leaves)
dc.identifier.citationMthembu, Siyanda Thabani (2018) Enaminone-based approaches to the synthesis of alkaloids possessing the pyrrolo[1,2-a]azepine core, University of the Witwatersrand, Johannesburg, <http://hdl.handle.net/10539/26053>
dc.identifier.urihttps://hdl.handle.net/10539/26053
dc.language.isoenen_ZA
dc.phd.titlePhDen_ZA
dc.subject.lcshPyrroles
dc.subject.lcshOrganic compounds--Synthesis
dc.titleEnaminone-based approaches to the synthesis of alkaloids possessing the pyrrolo[1,2-a]azepine coreen_ZA
dc.typeThesisen_ZA
Files
Original bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
S. T. Mthembu. 0202839H, PhD Abstract, 27th February 2018 (1).pdf
Size:
33.74 KB
Format:
Adobe Portable Document Format
Description:
Abstract
Download
No Thumbnail Available
Name:
S.T. Mthembu. 0202839H. Wits. PhD Thesis, 27th february 2018.pdf
Size:
9.61 MB
Format:
Adobe Portable Document Format
Description:
Main work
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
ETD Collection