Antibiotic resistance is becoming ever more severe due in part to the increasing use of antibiotic drugs. One significant contributor to this problem is the production of β-lactamase enzymes that provide resistance to common β-lactam antibiotics. The scope of this research is to synthesize and study the β-lactamase inhibitors of 2-carbamoyl-4-oxo-1,5-diazabicyclo [3.2.1] octane derivatives. Currently the research process is in the beginning stages of synthesizing three compounds: (R)-hexahydro-6-oxopyrimidine-4-carboxylic acid (1a), hexahydro-2,2-dimethyl-6-oxopyrimidine-4-carboxylic acid (1b) and hexahydro-6-oxo-2-phenylpyrimidine-4-carboxylic acid (1c). The future steps are to synthesize (R) -3-(methoxycarbonyl)-hexahydro-6-oxopyrimidine-4-carboxylic acid (2a), (R)-dimethyl tetrahydro-4-oxopyrimidine-1,6(2H)-dicarboxylate (3a) and (R)-methyl hexahydro-6-oxopyrimidine-4-carboxylate (4a). All the compounds will be evaluated for the inhibitory activities against pure TEM-1 and P99 β-lactamase.

Thesis (MSc (Chemistry and Biochemistry))--University of Limpopo, 2009. / Magnetic nanoparticles have been proposed for use as biomedical purposes to a large extent for several years. In recent years, nanotechnology has developed to a stage that makes it possible to produce, characterize and specifically tailor the functional properties of nanoparticles for clinical applications. This has led to various opportunities such as improving the quality of magnetic resonance imaging, hyperthemic treatment for malignant cells, site-specific drug delivery and the manipulation of cell membranes. To this end a variety of iron oxide particles have been synthesized. A common failure in targeted systems is due to the opsonization of the particles on entry into the bloodstreams, rendering the particles recognizable by the body’s major defense system, the reticulo-endothelial system. The co-precipitation method: nanoparticles comprised of gold shell and magnetite/maghemite inclusion were synthesized by overgrowing the gold shell onto the magnetic seeds using sodium citrates as a reducing agent. Oxidized magnetites (Fe3O4) fabricated by co-precipitation of Fe2+ and Fe3+ in strong alkaline solution were used as magnetic cores. These magnetic nanoparticles were characterized by X-ray diffraction (XRD), Transmission Electron Microscope (TEM), ultraviolet-visible (UV-vis) spectroscopy and Vibrating Sample Magnetometer (VSM). Results from x-ray diffraction show that the gold-iron oxide nanoparticles have a face-centered cubic shape, a=8.39 Å and a special group Fd3-m=227 with the dominant crystal planes of {311}. The gold-coated magnetic nanoparticles exhibited a surface plasmon resonance peak at 520 nm. The nanoparticles are well dispersed in distilled water. The particle size of the magnetite nanoparticles was about 0.5 μm (500 nm) confirmed by transmission electron microscope image. The saturation magnetization of the as-synthesized iron oxide nanopowders was 38 emu/g and the blocking temperatures for magnetization 1, magnetization 2, magnetization 3, and magnetization 4 are 150, 143, 138, and 135 K, respectively. The reverse micelle (Micro emulsion) method: a unique reverse micelle method has been developed to prepare gold-coated iron (Fe@Au) nanoparticles. X-ray diffraction, iv ultraviolet/visible, transmission electron microscope, and magnetic measurements are utilized to characterize the nanocomposites. X-ray diffraction only gives Face-Centered Cubic (FCC) patterns of gold for the obtained nanoparticles and indicated that gold exists as a metal. The absorption band of the iron@gold colloid shifts to a longer wavelength and broadens relative to that of the pure gold colloid. Transmission electron microscope results show that the average size of the iron@gold nanoparticles is about 2 μm (2000 nm) and indicated that the nanocomposite was single-nanosized and has a sharp size distribution. These nanoparticles are self-assembled into chains on micron scale under a 0.5T magnetic field. Magnetic measurements show that the particles are super paramagnetic with a blocking temperature (TB) of 42 K. At 300 K (above blocking temperature), no coercivity (Hc) and remanence (Mr) is observed in the magnetization curve, while at 2 K (below TB), coercivity and remanence are observed to be 728 Oe and 4.12 emu/g, respectively.

acase@tulane.edu / In Chapter 1 an overview of the field of water reduction catalysis is given, with an introduction to the concept of photo-catalytic water splitting. A background of the current research on molecular catalysts is also described. An introduction to the project is made detailing the approach to studying the molybdenum sulfide catalysts that were synthesized, characterized, and analyzed for this work. Chapter 2 describes in detail the synthesis and characterization of all the molybdenum sulfide complexes that were made. Initially looking at [Mo3S13]2- and later synthesizing derivatives of the type [Mo3S7(S2CNR2)3]+, [Mo3S4(S2CNR2)3]+, and [Mo3S4(S2CNR2)4]0 were successful. These complexes were characterized using 1H NMR, MALDI-TOF-MS, electronic absorption, and elemental analysis. A new ligand (S2CNiBu2) was also prepared for the synthesis of [Mo3S7(S2CNiBu2)3]+ complex. Chapter 3 lists all the crystal structures that were obtained for the ligands and metal complexes in this work. Metal complexes were purified using various crystallization techniques and identified and characterized. Starting from [Mo3S7(S2CNR2)3]+ complex type, the series included R = Et, Me, iBu, and 3,5-tBu(C6H3). A unique double cluster crystal structure was obtained after photolysis of [Mo3S7(S2CNiBu2)3]+ in the photosystem. The last set of four structures was found for the complex [Mo3S4(S2CNEt2)4]. Chapter 4 describes all the electro-chemical experiments and characterizations for all the metal complexes that were studied. Using cyclic voltammetry provided a starting point for understanding the behavior of these catalysts in catalytic experiments. Spectro-electrochemistry observes changes to the complexes during reductive processes and was used to test stability of the catalysts following reduction. Lastly, bulk electrolysis was used to test the electro-catalytic capability of the [Mo3S7(S2CNR2)3]+ catalysts. It was found that electrolysis at the second reduction potential yielded the highest faradaic yield for hydrogen. Chapter 5 introduces and describes the various types of photo-systems used in the field of photo-catalysis. Initial photo-catalytic experiments showed moderate activity of the [Mo3S13]2- and improvement was observed after preparing complexes of the type [Mo3S7(S2CNR2)3]+. Combining photolysis and MALDI-TOF-MS analysis revealed a transformation from the [Mo3S7(S2CNR2)3]+ cluster to [Mo3S4(S2CNR2)3]+ cationic complexes. After synthesizing and testing [Mo3S4(S2CNR2)3]+ and [Mo3S4(S2CNR2)4]0 species, they were not as efficient at generating hydrogen. / 1 / Patricia R. Fontenot

The total synthesis of cyanindin-3-glucoside (C3G) appropriate for ��C enrichment at C-1` and C-6` has been achieved for metabolic studies. Construction of the phenolic ring-B was achieved by a Diels-Alder reaction employing a novel diene, (2R,3R)-2,3-dimethyoxy-2,3-dimethyl-5,6-dimethylene-1,4-dioxane, which incorporates a butane diacetal protecting motif. Reaction with a (labelled) dienophile affords the protected catechol. Formation of the flavone skeleton was achieved by condensation of the benzamide (ring-B) with an acetophenone (ring-A). Esterification of the flavone skeleton in ring-A was found to be essential for oxidation at C-3 with dimethyldioxirane affording the flavonol. Glycosylation using a glucosyl bromide gave the β-adduct exclusively which was reduced to the target compound, C3G. The overall synthetic design permits the synthesis of the labelled anthocyanin in nine steps (23%) from the dienophile.

"October 1967." / Includes bibliographical references. / 151 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Propionyl-CoA carboxylase was purified from pig heart and a series of experiments were carried out to investigate some of the chemical and kinetic properties of the enzyme. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1967

Studies towards the total synthesis of (-)-gymnodimine (1), a marine neurotoxin with a unique molecular architecture and pronounced biological activity, are described. These studies resulted in a convergent approach to the advanced intermediate 315, containing the C3-C32 section of 1. Two synthetic routes were developed to construct the tetrahydrofuran subunit of (-)-gymnodimine. Both routes employed a highly stereoselective iodoetherification of alkenes 120 (initial route) and 158 (second generation route) to furnish cis-2,5- disubstituted tetrahydrofurans 121 and 159, respectively. The longest sequence in the second generation route required 16 linear steps to the tetrahydrofuran subunits. The initial approach needed 21 steps. Two cyclohexene subunits of (-)-gymnodimine, 246 and 265, were prepared from the Diels-Alder cycloadducts 213 and 214, respectively. The quaternary stereogenic center at C22 (gymnodimine numbering) of 236 was generated by the intramolecular lactonization of 235, which was obtained from 213. Assembly of two subunits, 146 and 299, employing a B-alkyl Suzuki-Miyaura reaction provided the coupled product 310 in good yield. After 310 was converted to the terminal alkyne 313, methylation of 313 was accomplished via a Stille reaction. In addition, a model study of the formation of the cyclic imine moiety of (-)-gymnodimine was carried out. / Graduation date: 2006

The rearrangement of a homoallyl cation to a cyclopropylcarbinyl cation is thought to play a role in the biogenesis of a variety of cyclopropane-containing natural products,¹ a hypothesis which has previously led to the design of successful biomimetic syntheses of several natural products.² The strategy underlying this approach to cyclopropane synthesis³ can be applied more broadly and would be particularly valuable if it could be extended to a set of contiguous cyclopropanes. This concept has led us to examine the rearrangement of certain homoallylic systems bearing a leaving group (triflate) at one terminus and a cation-stabilizing metal (tin) at the other. The effects of protecting groups of varying steric demand and of olefin geometry on the stereochemical outcome of the cyclization were examined. "Zipper" cyclization of (8R,5E,2Z)-1-tri-n-butylstannyl-9-trityloxy-nona-2,5-dien-8-ol (117) led to the stereoselective formation of three distinct bicyclopropane stereoisomers (110,111,112). The major diastereomer was isolated through derivatization and the absolute stereochemistry was verified by X-ray crystallography. The trans,syn,trans-bicyclopropane 118 was carried forward to complete a formal synthesis of the antifungal agent FR-900848 (49). The synthesis of a key precursor to halicholactone (188), neohalicholactone (189), and the solandelactones A-H (190-197) constructed around a transcyclopropane core is also described. The key steps in this synthesis are the stereoselective synthesis of trans-vinylcyclopropane 79, followed by a highly diastereoselective acetate aldol reaction leading to compound 269. / Graduation date: 2005

Studies toward the total synthesis of a highly potent cytotoxic marine natural product, phorboxazole A, were conducted and resulted in a route to an advanced intermediate, C4-C32, for this purpose. A key feature of our approach is the stereoselective synthesis of two cis-2,6-disubstituted tetrahydropyrans present in the macrolide portion of phorboxazole A by palladium (II) mediated intramolecular alkoxy carbonylation. This provided the C20-C32 and C9-C19 tetrahydropyran subunits of phorboxazole A. An attempt at diastereoselective formation of the third C5-C9 trans-2,6-disubstituted tetrahydropyran by hydride reduction of a C9 hemiketal was complicated by reduction of the C7 exocyclic olefin. However, the C5-C9 tetrahydropyran was constructed by an intramolecular etherification sequence using a novel allylsilane as the source of C4-C8 of the macrolactone. The studies carried out in the course of this thesis have set in place a major segment of the phorboxazole A structure; they require only the addition of the C1-C3 unit and minor functional group modifications to complete the macrolide portion of the molecule. / Graduation date: 2004

This dissertation details the investigation of an alternate pathway to isoprenoids that occurs in plants and microorganisms, the non-mevalonate pathway. This exploration of the pathway focuses on the second step, the conversion of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methylerythritol-4-phosphate (MEP) by the enzyme DXP isomeroreductase (DXR). These studies led to an appreciation of the stereochemical course of the enzymatic reduction step and to a better understanding of the structural requirements for inhibitors to have optimal interactions at the active site of the enzyme, DXR. The investigation of the reduction step mediated by DXR revealed that the C1 pro-S hydrogen in 2-C-methylerythritol-4-phosphate derives from C3 of DXP for the DXR from Synechocystis sp PCC6803. The pro-R hydrogen originates from NADPH. The pro-S hydride of NADPH is transferred to the re face of the proposed aldehyde intermediate, which designates DXR as a class B dehydrogenase. Based on the structural features of fosmidomycin, a known inhibitor of DXR, several analogs were synthesized and evaluated for their inhibitory activity against DXR. It was discovered that a polar head group with two ionizable groups, a suitable length of intervening carbons, and an N-acyl N-hydroxy moiety are important factors to demonstrate significant inhibition activity. These studies also provided information that is complementary to structural data obtained from recent X-ray crystal structures of DXR. / Graduation date: 2003

Regiochemistry of intramolecular [2+2] photocycloadditions of oxygenated 6-alkenyl-3-alkoxy-2-cyclohexenones is studied. Application of this methodology to construct a key intermediate [3.3.2] bicyclic skeleton of ryanodol is described as well. Irradiation of (3-butenyl)compounds 3, 11, 14 and of (4-pentenyl)compound 6 afforded exclusively the linear photoadducts 4, 12, 15 and 7 respectively. Irradiation of allyl compound 25 brought the desired crossed photoadduct 26. The structures of the photoadducts 4, 7 and 26 were assigned based on spectroscopic analysis and confirmed by subsequent retroaldol cleavage reactions of the corresponding photoproducts. The regiochemistry of linear adduct 15 was deduced by a sequence of transformations. Retroaldol cleavage of the photoadduct 15, followed by transannular reductive coupling with SmI���, and hydrolysis of the protecting group provided triol 18. PDC oxidation of 18 gave [4.2.2] bicyclic triketone 20 and a cyclic hemiketal 21. Finally, Swern oxidation of 18 confirmed both isomers of photoproduct 15 are linear adducts. Selective retroaldol ring opening of compound 26 resulted in the formation of the bicyclo[3.3.1]nonane skeleton, amenable through a one carbon ring expansion to establish the core bicyclo[3.3.2]decane system in ryanodol. / Graduation date: 1998