Student Number : 9201775F - MSc dissertation - School of Chemistry - Faculty of Science / The base/light-induced cyclisation (condensation) reaction between alkyl and carbonyl substituents on biaryl compounds discovered in the University of the Witwatersrand laboratories was used to synthesise benzo[c]carbazoles. Specifically, 5,7-dimethyl-7H-benzo[c]carbazole was synthesised from 2-methyl-1H-indole in 79 % yield over four steps. The reaction sequence involved bromination of 2-methyl-1H-indole at C-3 to give 3-bromo-2-methyl-1H-indole. The subsequent methylation of the amino group to give 3-bromo-1,2-dimethyl-1H-indole was followed by Suzuki coupling with acetophenone-2-boronic acid under non-aqueous reaction conditions to give 1-[2-(1,2-dimethyl-1H-indol-3-yl)phenyl]. Lastly, tBuOK/hν–induced cyclisation of the product yielded the desired benzo[c]carbazole. 10-Methoxy-5,7-dimethyl-7H-benzo[c]carbazole was synthesized analogously in 75% yield from 5-methoxy-2-methyl-1H-indole.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. January 1996. / Aspects of the literature of the ant venom alkaloid monomorine I and its stereoisomers were reviewed. Racemic 5-butyl-2-pyrrolidinone was synthesised in two steps from methyl acrylate and 1-nitropentane, A thionation step yielded 5-butylpyrrolidine-2-thione. The Michael addition reaction between 5-butylpyrrolidine-2-thione and ethyl crotonate proceeded with difficulty to form a separable mixture of diastereomers of 5-butyl-l-(2-ethoxycarbonyl-l-methylethyl) pyrrolidine-2-thione. [Abbreviated Abstract. Open document to view full version] / AC2017

This thesis describes a novel total synthesis of (±)-dehalo-perophoramidine (a dehalogenated analogue of the natural product perophoramidine). The key synthetic transformation involves the construction of vicinal quaternary stereocenters which were installed diastereoselectively. A Claisen rearrangement was used to install the first quaternary stereocenter then a Corey-Chaykovsky-type reaction and a Hosomi-Sakurai-type reaction were used to install the second quaternary stereocenter. Investigations directed towards the total synthesis of the communesin family of natural products are also described. In Chapter 1, the natural products perophoramidine and the communesins are introduced and their related biosynthesis is discussed. The isolation, architectural motifs and biological properties of the natural products are described and discussed. Previously reported approaches to perophoramidine and the communesins are reviewed focussing on how the vicinal quaternary stereocenters are formed in each case. Chapter 1 concludes with the retrosynthetic plan used to form dehalo-perophoramidine. In Chapter 2, previous research from the Westwood group is reviewed focusing on an asymmetric Claisen rearrangement which could potentially be used to install a quaternary stereocenter asymmetrically. A previously reported novel Cope rearrangement, potentially useful for a communesin synthesis, is optimised using microwave, neat and high-temperature flow conditions and leads to the synthesis of an intermediate containing two allyl substituents. In Chapter 3, attempts to functionalise selectively the two allyl substituents are described which was eventually achieved by a regioselective iodoetherification reaction. This leads to the synthesis of two relatively advanced intermediates for a communesin synthesis. Although the total synthesis of the communesins was not achieved, a proposed route from the advanced intermediates to the natural products is described. In Chapter 4, a novel method to construct vicinal quaternary stereocenters is disclosed using a Corey- Chaykovsky-type reaction and a Hosomi-Sakurai-type reaction. A regioselective iodolactonisation, analogous to that presented in Chapter 3, is used to functionalise selectively two allyl substituents that culminates in the preparation of a pentacyclic lactam. In Chapter 5, the total synthesis of (±)-dehalo-perophoramidine is completed and its structure is confirmed by a NMR doping experiment with an authentic sample. The biological activity of dehalo- perophoramidine is investigated and compared to that of perophoramidine. Chapter 5 culminates in an attempted synthesis of the natural product perophoramidine using the route that was used to make dehalo-perophoramidine.

Dan Dan Ho. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 134-144). / Chapter Chapter One --- Introduction --- p.1 / Chapter 1.1 --- Phytochemistry and Phylogeny --- p.1 / Chapter 1.2 --- Biological Activity --- p.9 / Chapter 1.3 --- Synthetic Estrogens and Anti-Estrogens --- p.14 / Chapter 1.4 --- Estrogen Receptor and Anti-Estrogen Binding Site --- p.19 / Chapter 1.5 --- Multiple and dissociated Biological Activity --- p.28 / Chapter 1.6 --- A Future Role for Yuehchukene --- p.30 / Chapter Chapter Two --- Materials and Methods --- p.35 / Chapter 2.1 --- Chemical Synthesis --- p.35 / Chapter 2.1.1 --- Synthesis of Yuehchukene --- p.35 / Chapter 2.1.2 --- Substitution of Yuehchukene --- p.38 / Chapter 2.1.2.1 --- Substitution at N-1' and N-5 --- p.38 / Chapter 2.1.2.2 --- Substitution at C2-C5 --- p.45 / Chapter 2.1.2.3 --- Saturation of C9-C10 Double Bond --- p.45 / Chapter 2.1.2.4 --- Aromatic Hydroxylation --- p.45 / Chapter 2.1.2.5 --- Synthesis of Benzofuran-3-HMBI --- p.47 / Chapter 2.1.3 --- Stereo-selective Synthesis of R(+)- and S(-)-Camphor-yuehchukene --- p.47 / Chapter 2.1.4 --- Instruments --- p.51 / Chapter 2.2 --- Bioassay --- p.51 / Chapter 2.2.1 --- Anti´ؤimplantation Activity --- p.52 / Chapter 2.2.2 --- Uterotrophic Activity --- p.52 / Chapter 2.2.3 --- Blue Test --- p.53 / Chapter 2.2.4 --- Binding Assays --- p.54 / Chapter 2.2.4.1 --- Uterine Cytosolic Estrogen Receptor Binding Assay --- p.54 / Chapter 2.2.4.2 --- Liver Microsomal Fraction Anti-Estrogen Receptor Binding Assay --- p.55 / Chapter 2.2.5 --- Enzyme Activity --- p.56 / Chapter 2.2.5.1 --- Ornithine Decarboxylase Activity Assay --- p.56 / Chapter 2.2.5.2 --- Glucose-6-Phosphate Dehydrogenase Activity Assay --- p.58 / Chapter 2.2.6 --- Cell Culture --- p.59 / Chapter 2.2.6.1 --- MCF-7 Cell Line --- p.59 / Chapter 2.2.6.2 --- Growth Response Studies --- p.59 / Chapter 2.3 --- Exhibit I --- p.61 / Exhibit II --- p.62 / Exhibit III --- p.63 / Exhibit IV --- p.64 / Exhibit V --- p.65 / Chapter Chapter Three --- Results --- p.66 / Chapter 3.1 --- Chemical Synthesis --- p.66 / Chapter 3.1.1 --- Yuehchukene --- p.66 / Chapter 3.1.2 --- Substitution of Yuehchukene --- p.67 / Chapter 3.1.2.1 --- Substitution at N-1' and N-5 --- p.67 / Chapter 3.1.2.2 --- Substitution at C2 and C5 --- p.69 / Chapter 3.1.2.3 --- Saturation of C9-C10 Double Bond --- p.70 / Chapter 3.1.2.4 --- Aromatic Hydroxylation --- p.71 / Chapter 3.1.3 --- Stereo-selective Synthesis of R(+)- and S(-)-Camphor-yuehchukene --- p.72 / Chapter 3.2 --- Bioassay --- p.72 / Chapter 3.2.1 --- Anti-implantation Activity --- p.72 / Chapter 3.2.2 --- Uterotrophic Activity --- p.87 / Chapter 3.2.3 --- Blue Test --- p.88 / Chapter 3.2.4 --- Binding Assays --- p.93 / Chapter 3.2.4.1 --- Uterine Estrogen Receptor [3H]-Estradiol Binding Assay --- p.93 / Chapter 3.2.4.2 --- Liver Microsomal Anti-Estrogen Binding Site [3H] -Tamoxifen Binding Assay --- p.93 / Chapter 3.2.5 --- Enzyme Activity --- p.96 / Chapter 3.2.5.1 --- Ornithine Decarboxylase Activity Assay --- p.96 / Chapter 3.2.5.2 --- Glucose-6-Phosphate Dehydrogenase Activity Assay --- p.96 / Chapter 3.2.6 --- MCF-7 Cell Growth Response --- p.99 / Chapter Chapter Four --- Discussion --- p.102 / Chapter 4.1 --- Species Specificity --- p.102 / Chapter 4.2 --- Estrogenic Indoles --- p.104 / Chapter 4.3 --- Conservative Structure --- p.108 / Chapter 4.4 --- Hydroxylation Sites --- p.111 / Chapter 4.5 --- Configuration and Constraints --- p.114 / Chapter 4.6 --- Dissociated Responses --- p.128 / Chapter 4.7 --- Summary --- p.132 / References --- p.134

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1981. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographical references. / by Paul Hsiao-tseng Liang. / Ph.D.

Graduation date: 1994

Fatty acid synthase (FAS), an enzyme that is over-expressed in many cancers, is necessary for cancer cell proliferation. Previously, we have shown that FAS in cancer cells is regulated at least in part, by Sp1. Indole-3-carbinol (I3C) and its acid condensation product, 3,3’-diindolylmethane (DIM) modulate various transcription factors involved in regulating cellular proliferation and apoptosis. The objective of this study was to determine whether reductions in breast cancer cell proliferation caused by I3C and/or DIM occur as a result of reductions in FAS. DIM and, in some cases, I3C reduced FAS expression in three breast cancer cell lines. However, addition of palmitate or oleate to DIM-treated MCF-7 cells did not restore proliferation. DIM-associated reduction in proliferation of MCF-7 cells also results in a reduction of Sp1 expression, and down-regulation of FAS occurs after inhibition of proliferation. Thus, the anti-proliferative effect of I3C and DIM may be due to their effect on down-regulating Sp1, which in turn could modify several Sp1-associated genes, including FAS.

Fatty acid synthase (FAS), an enzyme that is over-expressed in many cancers, is necessary for cancer cell proliferation. Previously, we have shown that FAS in cancer cells is regulated at least in part, by Sp1. Indole-3-carbinol (I3C) and its acid condensation product, 3,3’-diindolylmethane (DIM) modulate various transcription factors involved in regulating cellular proliferation and apoptosis. The objective of this study was to determine whether reductions in breast cancer cell proliferation caused by I3C and/or DIM occur as a result of reductions in FAS. DIM and, in some cases, I3C reduced FAS expression in three breast cancer cell lines. However, addition of palmitate or oleate to DIM-treated MCF-7 cells did not restore proliferation. DIM-associated reduction in proliferation of MCF-7 cells also results in a reduction of Sp1 expression, and down-regulation of FAS occurs after inhibition of proliferation. Thus, the anti-proliferative effect of I3C and DIM may be due to their effect on down-regulating Sp1, which in turn could modify several Sp1-associated genes, including FAS.

There is a need in the cotton industry for cultivars with enhanced lint yield potential and high-quality fiber properties. Indole-3-acetic acid (IAA) is a phytohormone that is predominantly responsible for cell elongation and required for primary elongation in cotton fiber development. An increase in IAA at specific fiber developmental stages may promote increased lint percent and longer fibers. Objectives of this research project were to determine how exogenous applications in a field environment affect fiber traits and lint yield potential in diverse genotypes. The first study examined application methods to ascertain the optimal placement and timing of IAA. The second study focused on genotype reactions to elevated levels of IAA. Results indicate exogenously applied IAA provided a potential yield increase but did not improve fiber length. Further research needs to be conducted to effectively understand IAA’s role in fiber development and establishing protocols for maximizing IAA potential in a field environment.

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