Synthesis and Characterization of Organic and Inorganic Compounds with Biological Applications Open Access

Wein, Alexander (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/n870zr46x?locale=en
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Abstract

Progress towards the synthesis of two families of anti-cancer drugs is reported. Gold(III) complexes were made with bidentate amine ligands and tested for DNA binding, thioredoxin reductase inhibition, stability against biological reductants, and cytotoxicity. The results suggest that contrary to current opinion, the cytotoxicity of these types of complexes is not solely due to thioredoxin reductase inhibition and appears to occur via several different processes.

A synthetic route to novel sphingolipids is also reported. These are made by a three part convergent synthesis that allows for control of the stereochemistry of the hydrophilic head. From one highly unsaturated sphingolipid it is possible to selectively reduce and oxidize the molecule to several different compounds allowing for an extended family of conformationally constrained compounds to be made via a subsequent divergent synthesis.

Also reported are a new synthesis of 4-trimethylsilyl-2-butyn-1-ol and a study of the 19F NMR and solid state characteristics of fluorinated copper(II) carboxylates.

Table of Contents

Table of Contents
I. Synthesis and Characterization of 5,6-Disubstituted Phenanthroline-Gold(III) Compounds as Anti-Tumor Agents

1. Introduction...1
2. Results and Discussion...5

2.1. Synthesis and Characterization...5
2.2. Biological Activity...7

2.2.1. DNA Binding...7
2.2.2. TrxR Inhibition...9
2.2.3. Cytotoxicity...10

2.4. Stability Studies...15

3. Conclusions...17
4. Experimental...18

4.1. General Experimental Procedures...18

4.2.1. 5,6-Dimethyl-1,10-phenanthroline (1, 56DMP)...19
4.2.2. Benzo[f]-1,10-phenanthroline (2, BP)...19
4.2.3. Dichloro-5,6-dimethyl-1,10-phenanthrolineaurate(III) tetrafluoroborate (3, 56DMPAuCl2+)...20
4.2.4. Dichloro-benzo[f]-1,10-phenanthrolineaurate(III) tetrafluoroborate (4, BPAuCl2+)...21

4.3. DNA Binding...21
4.4. Thioredoxin Reductase Inhibition Studies...22
4.5. Cytotoxicity Assays...22

II. Towards the Synthesis of Conformationally Constrained Sphingosine Analogues

1. Introduction...24
2. Results and Discussion...29
3. Conclusion...31
4. Experimental...32

4.1. General Experimental Procedures...32
4.2. (Z)-But-2-en-1-ol (1)...32
4.3. ((2S,3R)-3-Methyloxiran-2-yl)methanol (2)...32
4.4. (2R,3S)-3-Azidobutane-1,2-diol (3)...34
4.5. ((3-(Hex-1-yn-1-yl)phenyl)ethynyl)trimethylsilane (4)...34
4.6. 1-Ethynyl-3-(hex-1-yn-1-yl)benzene (5)...35

III. A More Economical Synthesis of 4-Trimethylsilyl-2-butyn-1-ol

1. Introduction...37
2. Discussion...37
3. Procedure...38

2.1 Characterization Data...40

IV. Synthesis and Characterization of Copper(II) Paddlewheel Complexes Possessing Fluorinated Carboxylate Ligands

1. Introduction...41
2. Results and Discussion...43

2.1 Synthesis...43
2.2 IR...44
2.3. 19F NMR...45
2.4. Crystal Structures...48

3. Conclusion...53
4. Experimental...53

4.1. General Procedures...53

4.1.1. General procedure for synthesis of copper(II) aryl carboxylate salts...54
4.1.2. General procedure for synthesis of copper(II) alkyl carboxylate salts...55

4.2. Characterization data for compounds 1-6...55

4.2.1. Bis[(2-fluorobenzoate])copper(II) (1)...55
4.2.2. Bis[(3-fluorobenzoate)]copper(II) (2)...55
4.2.3. Bis[(4-fluorobenzoate)]copper(II) (3)...56
4.2.4. Bis[(3,3,3-trifluoropropionate)]copper(II) (4)...56
4.2.5. Bis[(3-(trifluoromethyl)butyrate)]copper(II) (5)...56
4.2.6. Bis[(5,5,5-trifluoropentanoate)]copper(II) (6)...56

5. Notes...56

V. References...58


Figures and Tables

Figure 1.1...1
Figure 1.2...2
Figure 1.3...5
Scheme 1.1...6
Figure 1.4...7
Figure 1.5...9
Figure 1.6...9
Figure 1.7...10
Table 1.1...10
Figure 1.8...12
Figure 1.9...13
Figure 1.10...13
Figure 1.11...14
Figure 1.12...14
Figure 1.13...15
Table 1.2...15
Figure 1.14...16
Figure 1.15...17
Figure 1.16...17
Figure 2.1...25
Figure 2.2...25
Figure 2.3...26
Figure 2.4...27
Scheme 2.1...28
Scheme 2.2...29
Scheme 2.3...30
Scheme 2.4...31
Scheme 2.5...32
Table 2.1...34
Scheme 3.1...37
Scheme 4.1...43
Table 4.1...44
Table 4.2...46
Figure 4.1...47
Figure 4.2...50
Figure 4.3...51
Figure 4.4...51
Figure 4.5...52

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