Browsing by Subject "Organic chemistry."
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Item Discovery of DNA-enzymes dependent on small-molecule cofactors; design, synthesis and evaluation of TLR-7 agonists and their immunoprotein conjugates.(2010-10-08T16:26:39Z) Romero, José Roberto Boquín.; Kane, Robert R.; Chemistry and Biochemistry.; Baylor University. Dept. of Chemistry and Biochemistry.Several catalytic families of DNA enzymes (deoxyribozymes) have previously been isolated through the use of an in vitro selection technique in our laboratory. The activities of these deoxyribozymes appear to be dependent upon the presence of a small organic cofactors. To further characterize these catalytic oligonucleotides, the organic cofactors were re-synthesized and background cleavage experiments were performed in the absence of the enzymatic sequence. Several studies were performed to improve the background cleavage experiment by reacting several variants of the substrate under different conditions. Additionally, enzymatic sequences from the literature were also examined to test the accuracy of our methodology. Results from the background cleavage experiments showed that in the absence of a DNA enzyme, cleavage of the oligonucleotide substrate is almost negligible. In an attempt to isolate new families of deoxyribozymes, an in vitro selection was performed using two concentrations of a new synthetic cofactor. Unfortunately, after eleven rounds of selection, the catalytic activity of the oligonucleotide pool did not improved substantially. In a second project, several adenine derivatives were synthesized as toll-like receptor 7 agonists. These molecules were functionalized for their conjugation to a protein through the use of a heterobifunctional protein linker. The synthesis of these toll-like receptor agonists required a multi-step synthetic route. In vitro studies evaluation of some of these compounds showed excellent potency at inducing cytokine production. An antibody conjugate of one compound, targeted to an internalizing dendritic cell receptor, demonstrated exceptional activity that exceeded the free agonist or the agonist targeted to a non-relevant receptor.Item The origin of remarkable chromatographic differences in novel azulenyl-1,5-diols and synthesis and use of phosphinine and phosphabarrelene ligands for asymmetric catalysis.(2014-09-05) Horgen, Dana Ann; Garner, Charles M. (Charles Manley), 1957-; Chemistry and Biochemistry.; Baylor University. Dept. of Chemistry and Biochemistry.The synthesis, characterization and analysis of novel chiral molecules advance many areas of synthetic organic chemistry, both industrially and academically. This work touches on three of the major methods for obtaining enantiomerically pure compounds. Based on the observation of a remarkably large difference in the silica TLC mobility of a pair of azulene 1,5-diol diastereomers, a series of such azulene 1,5-diols were prepared. Every pair of diastereomers was especially well separated, and X-ray crystallography revealed a conformational explanation of the large differences in mobility. The separation of the diol enantiomers was then studied on two chiral HLPC columns. The enantiomers were well-resolved, the separation appearing to benefit from the presence of the azulene ring. In addition, the more polar diastereomers on silica TLC gave dramatically better enantiomer separations on a Chiralcel-OD-H column. Very few chiral phosphinine and phosphabarrelene ligands have been reported in the literature but have shown promise as good ligands for asymmetric catalysis. Our group had previously synthesized a C₂-symmetric chiral bis-camphorphosphinine and the derived bis-camphorphosphabarrelene but neither had been tested as ligands for hydroformylation. In this work, optimization of the synthesis of these two compounds was undertaken. In addition, modifications to the structure of these molecules that incorporated electron donating (N,N-dimethylaminophenyl-) or electron withdrawing (trifluoromethyl-) substituents were made in an attempt to affect the electronic nature of the phosphorus atom. Steric modifications were also done to create a more hindered environment around the phosphorus atom. The activity and selectivity of bis-camphorphosphinine, bis-camphorphosphabarrelene and other chiral phosphinine molecules serving as ligands in the rhodiumcatalyzed hydroformylation of styrene were compared to other phosphorus ligands recently published in the literature. All of these ligands gave complexes that have moderate activity with good regioselectivity but very little enantioselectivity. Therefore, more tuning of these ligands' properties need to be done in order to achieve the activity and selectivity of other chiral monodentate-ligands. The bis-camphorphosphabarrelene was also a successful organocatalyst of the Baylis-Hillman reaction, showing its versatility in both metal-catalyzed and metal-free catalysis.Item Synthesis and application of C₂ asymmetric phosphinines via their pyrylium salt precursors.(2010-06-23T12:17:11Z) Bell, Jason R.; Garner, Charles M. (Charles Manley), 1957-; Chemistry and Biochemistry.; Baylor University. Dept. of Chemistry and Biochemistry.The development of new chiral ligands for asymmetric catalysis is an increasingly important area of research. Though many ligands are phosphorus based, one class of phosphorus ligands, phosphinines (phosphabenzenes), have been little studied. Most studies of chiral phosphinines, especially for those used in asymmetric catalysis have involved essentially attaching achiral phosphinines to chiral auxiliaries. The synthesis of the first C₂ chiral phosphinine was accomplished by converting (+)-camphor to the corresponding pyrylium salt, and then converting the pyrylium to the phosphinine. Though several initial attempts failed at forming the necessary pyrylium salt using simpler synthetic methods, an effective route for forming the pyrylium was chosen utilizing the preformed 3-ene-1,5-dione precursor. The camphor-based phosphinine was fully characterized and applied to two asymmetric catalytic test reactions, asymmetric hydrosilylation and asymmetric hydrogenation. Though (+)-camphor provided a convenient, cost-effective, and enantiomerically pure starting material, nature provides few compounds fitting all the necessary requirements for the starting materials. Therefore, derivatized cyclohexanones were also synthesized. Specifically, pyryliums salts based on 2-methyl-2-phenylcyclohexanone were synthesized, albeit in low yield. Attempts to use the improved synthetic method developed for the camphor-based pyryliums failed at the chlorination stage. Attempts to convert the (+)-camphor chlorobenzylidene intermediate into C₁ chiral pyryliums also failed. The C₂ asymmetric phosphinine based on camphor did react with benzyne to yield a new chiral phosphabarrelene.