Polyketides are a group of complex natural products that can inhibit the growth of bacteria, viruses, fungi, and tumor cells. Most polyketides are very difficult to extract from bacteria. Therefore, numerous syntheses of polyketide-related synthons have been attempted. <p> However, controlling the stereochemistry of the polyketide poses the most challenging task for researchers. The aim of this report is to discuss control of the stereochemistry of the polyketide-related synthons in asymmetric aldol reactions. Several important methodologies for stereochemical control in the aldol reaction exist. The first approach is to control the enolate geometry and the aldehyde (or ketone) geometry. The second approach is to use a chiral auxiliary and chiral ligands. The third approach is to use a chiral catalyst, which is the most efficient method if the catalyst operates with complete efficiency. Proposed transition states are also described to explain the resulting stereochemistry of the aldol adduct. / Master of Science

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第19515号 / 理博第4175号 / 新制||理||1599(附属図書館) / 32551 / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 大須賀 篤弘, 教授 依光 英樹 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

<p> Experimental and theoretical investigations on charge dependence and charge asymmetry in N-N and λ-N interactions are reviewed. The γ-π-exchange N-N and λ-N potentials are derived and calculated in the static limit. The γ-π-exchange charge dependent component of the N-N potential is found to be larger than the charge dependent part of OPEP due to pion mass difference up to 3 fm and is of opposite sign, making the explanation of the splitting between p-n and p-p scattering lengths more difficult than was previously thought. Except at very short distances, this potential is of the order of only a few percent of the OPEP. In the light of this result, it is concluded that the very large charge-dependent correction at large distances required by Noyes' phenomenological analysis on the splitting of rpn and rpp is inexplicable as an electromagnetic correction. The γ-π exchange charge asymmetric components of both N-N and λ-N interactions are found to be much weaker than the charge dependent one for the N-N case.</p> / Thesis / Doctor of Philosophy (PhD)

Keratoconus is an eye disease that manifests as progressive thinning and steepening of the cornea. While there is no singular cause for keratoconus, both genetic and environmental factors have been proposed to influence the onset and progression. This review aims to explore the pathogenesis, identification, classification, and treatment of this corneal disease. Since early detection is essential in treatment success, various imaging methods have been developed to analyze multiple aspects of the corneal surface. Keratoconus can be identified with a reflection based system, elevation based system, as well as a combination of the two. Once diagnosed, the Belin ABCD classification can be used to monitor the stage of keratoconus and treat it accordingly. Current treatment options prioritize halting disease progression with corneal crosslinking before considering visual rehabilitation. Individuals with mild keratoconus can improve vision with non-surgical options such as spectacles and contact lenses. As the disease progresses, patients may need surgical intervention such as intrastromal corneal ring segments or photorefractive keratectomy (PRK). In advanced keratoconus cases, the cornea may need to be replaced with partial or full-thickness keratoplasty. The goal of this review is to evaluate the more current treatment options that have become available today.

There are numerous classes of N-heterocyclic carbenes (NHCs) that have been synthesized since the discovery of stable NHCs in 1988. Their application as ligands in metal complexes has received much attention because of their strong sigma-donor and poor pi-acceptor properties. Within these NHC metal complexes, we are interested in studying zirconium metal complexes with pincer NHC ligands. Recently, achiral CCC-NHC pincer zirconium complexes were synthesized and their catalytic activity in intramolecular hydroamination of aminoalkenes were reported. Herein is reported new reaction conditions which yield pure, chiral CCC-NHC Zr pincer mono(amido) dibromo complex. The enantiopure crystal structure of the same complex is reported. Attempts to synthesize chiral CCC-NHC Zr pincer bis- and tris- amido complexes with the iodo salt of the ligand precursor are summarized. Moreover, syntheses of chiral bis(imidazolinium) ligand precursors with different counter anions are reported with optimized reaction conditions.

Modern organic synthesis typically centers around the use of expensive, complex, homogeneous catalyst systems in organic solvents which often generate copious amounts of hazardous waste. Therefore, the development of water-tolerant catalysts capable of performing reactions in aqueous solutions has become a growing area of scientific inquiry. To this end, we have designed and optimized a water-stable catalyst (Mn[TMPyP4]I5) capable of generating aziridines from olefins in aqueous solutions. Aziridines are valuable synthetic building blocks that have been used to generate various biologically active compounds, though synthetic techniques for aziridine synthesis are not well-established. Our ultimate goal was developing a catalytic system, which could be paired with DNA in order to perform asymmetric transformation in aqueous solutions. Herein we report the optimization of reaction conditions using Mn[TMPyP4]I5 paired with various DNA types, in the hopes of generating chiral aziridines from several olefinic substrates.

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This thesis describes the synthesis of functionalized spiroligomers and their applications in metal binding, metal-mediated catalysis, and organocatalysis. By synthesizing a family of functionalized bis-amino acids achieved from reductive alkylation, the Schafmeister group has developed access to highly functionalized and shape programmable structures named “spiroligomers.” The rigid backbones of spiroligomers are good at organizing the orientations of functional groups on their side chains. This property enables them as promising candidates for catalysts. Firstly we synthesized a few spiroligomer dimers presenting metal-binding groups such as terpys and bipys. With the right orientation of metal binding groups controlled by adjusting the stereocenter of the spiroligomer, macrocyclic “square” complexes with metals were obtained. The crystal structures of these intriguing complexes were solved. This work rendered the first structurally, spectroscopically and electronically characterized metal-spiroligomer complexes as well as the first crystal structure of spiroligomer. Secondly, the question of whether metal-binding spiroligomers are able to catalyze certain reactions became our major concern. We developed a binuclear copper catalyst that could accelerate a phosphate ester rearrangement, and that demonstrated that when the two copper binding terpyridine groups were best able to approach each other, they accelerated the rearrangement more than 1,000 times faster than the background reaction. Other molecules that did not properly organize the two copper atoms demonstrate considerably slower reaction rates. At last, catalysts based on spiroligomers without metals are also of interests. By displaying two hydrophobic groups in various directions on a monomeric spiroligomer (also can be regarded as a proline derivative), we observed variable activities and enantioselectivities in the catalysis of asymmetric Michael addition (up to 94% ee at -40 °C for one organocatalyst). / Chemistry

Bis(diphenylphosphino)amine (PNP) ligands, prepared from (S)-(-)-1-methylbenzyl amine, (-)-cis-myrtanylamine, (S)-(-)-1,1-napthyl(ethyl)amine (PNP1 1a, PNP2 1b, and PNP3 1c respectively) and their cobalt carbonyl complexes are reported. In the absence of alkynes the PNP ligands chelate to the cobalt rather than bridging the two cobalt centers. Although the PNP ligands are chiral the crystal structures are best solved in centrosymmetric space groups with disorder at the chiral carbon with the exception of (PNP3)Co2(CO)6, 2c, which is solved in a non-centrosymmetric space group. When the PNP ligand chelates to cobalt, as in 2, the compounds show activity for the catalytic Pauson-Khand reaction, whereas when the PNP ligand bridges, as in 3, the reaction precedes stiochiometrically. The use of these chiral ligands has not yet resulted in enantioselective catalytic Pauson-Khand cycloadditions. However, a small 15% e.e. was detected for the stiochiometric Pauson-Khand cycloaddition with 3c as the metal substrate. / Master of Science