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A rhodium-catalyzed process has been developed in which mixtures of internal and terminal olefins are isomerized and hydroborated in one step yielding the corresponding terminal pinacolboronates. Homologation and subsequent oxidation regiospecifically affords the terminal aldehyde in what amounts to a one-pot CO free hydroformylation. Good overall yields are obtained in all substrates examined. In a related study, mechanistic aspects of the rhodium catalyzed hydroboration of vinyl arenes have been probed. A combination of substituent effects (Hammett study), deuterium labeling studies and heavy atom isotope effects has demonstrated mechanistic differences in the hydroboration of electron rich and electron poor substrates. The results of the study further demonstrate the differences in reaction mechansim for hydroborations mediated with catecholborane versus pinacolborane. The Corey-Chaykovsky reaction, in which an aldehyde and a sulfur ylide are coupled to yield an epoxide has proven to be a versatile and valuable method for the production of epoxides. The reaction between benzaldehyde and benzyldimethylsulfonium tetrafluoroborate has been subjected to a kinetic analysis. Activation parameters were determined for the reaction and a large negative ΔS‡ of -35 cal/mol/K was calculated for the epoxidation of benzaldehyde. A large carbon kinetic isotope effect of 1.026 and an inverse deuterium isotope effect of 0.93 were determined for the reaction. A large positive Hammett ρ of +2.50 was found for the epoxidation of various substituted benzaldehydes by competition experiments. These results aided in the identification of the rate limiting step as addition of the ylide species to benzaldehyde. In a separate, although related study, the mechanism of the collapse of hydroxysulfonium salts has been examined with regard for implications in the epoxidation of aldehydes. The anti-diastereomer reacted with complete retention of stereochemistry and no crossover, while the syn-diastereomer gave crossover products along with cis and trans epoxides. Deprotonation and re-protonation on the carbon of the alpha-hydroxy sulfonium ylide was responsible for production of the trans epoxide as demonstrated by deuterium labeling. / Thesis (Ph.D, Chemistry) -- Queen's University, 2007-08-29 17:56:36.642

Carbohydrates constitute the most abundant class of natural products in the living world and they play various roles. They are notably involved in cell-cell interactions and immune reactions. It has been observed that tumor cells express, on their surface, unusual oligosaccharides named Tumor-Associated Carbohydrate Antigen (TACA). One TACA of interest to our research group is the Lewis A Lewis X hexasaccharide that is displayed on the surface of squamous lung carcinoma cells. Since carbohydrates are involved in immune reactions and can be recognized by antibodies, it becomes possible to design a carbohydrate-based vaccine against these tumor cells. This thesis describes the total synthesis of the TACA Lewis A Lewis X hexasaccharide and the preparation of two fragments: one tetra- and one pentasaccharide. These molecules were prepared as hexyl and aminohexylglycosides. In addition, the hexasaccharide was synthesized as a disulfide. This diversity of these synthons will allow conjugation to a protein, analysis by nuclear magnetic resonance techniques, and immobilization on gold of the antigen. Without doubt, this work is a significant contribution to the development of an anti cancer vaccine as it constitutes the first stage of the process.

Cellulose is an extraordinarily abundant polymer that can be harvested and purified from trees and other renewable sources. Cellulose derivatives have been widely used as coatings, optical films, fibers, molded objects, and matrices for controlled release. The properties of cellulose derivatives are not only affected by the degree of substitution, but also by the position of substitution. In order to establish the structure-property relationships of cellulose derivatives, it is of great importance to impart regioselectivity into functionalized cellulose. However, regioselective substitution of cellulose is extremely challenging, especially in the synthesis of regioselectively functionalized cellulose esters due to the unstable ester bond under aqueous alkaline or acid conditions. In this dissertation, the main objective is to search for new tools to synthesize regioselectively substituted cellulose esters, to understand how structural changes impact properties and performance, and thus to design cellulose derivatives delivering high performance. Several strategies for regioselective preparation of cellulose esters are discussed in detail. The obtained regioselective cellulose esters were fully characterized analytically. / Ph. D.

Based on reactions with two flavanones, three flavonols, and five flavones the regioselectivities of twelve human UDP-glucuronosyltransferase (UGT) isozymes were elucidated. The various flavonoid glucuronides were differentiated based on LC-MS/MS fragmentation patterns of [Co(II)(flavonoid – H)(4,7-diphenyl-1,10-phenanthroline)2]+ complexes generated upon post-column complexation. Glucuronide distributions were evaluated to allow a systematic assessment of the regioselectivity of each isozyme. The various UGT enzymes, including eight UGT1A and four UGT2B, displayed a remarkable range of selectivities, both in terms of the positions of glucuronidation and relative reactivity with flavanones, flavonols and flavones. The UGT1A enzyme selectivities are affected by the presence of a hydroxyl group at the 3, 6, 4’, or 3’ positions as well as by the presence of a methoxy at the 3’ position. The UGT2B enzymes show poor to no reactivity with the flavonols or flavones. This result implies that the greater planarity of the flavonols and flavones compared to structure of flavanones inhibits interaction with the UGT2 enzymes. For baicalein and scutellarein, three of the UGT1A isozymes (1A8, 1A9, and 1A10) resulted in the formation of 6-O glucuronides, enabling the fragmentation rules for the metal complexation/MS/MS strategy to be expanded. / text

Chemical modification of cellulose has been of growing interest, owing to the abundance and processing challenges of natural cellulose. To date, etherification and esterification are the most effective strategies to modify physicochemical properties of cellulose and append new functionalities. However, they typically require relatively harsh conditions, thus limiting introduction of new functional groups. An alternative strategy to synthesize novel cellulose derivatives is to append a good leaving group to cellulose backbone, followed by nucleophilic substitution reaction. Though tosylation and bromination of cellulose are frequently used, they have drawbacks such as chemo- and regioselectivity issues, high cost, and difficulty in purification. We have successfully developed a method to chemo- and regioselectively chlorinate cellulose esters using MsCl. Compared to bromination of cellulose typically used, this chlorination method has many advantages, including low cost of reagents and ease of separation. The chlorinated cellulose esters are useful intermediates for appending new functionalities by displacement reactions. We have synthesized a library of cellulose ester derivatives by this chlorination/nucleophilic substitution strategy, including cationic and anionic cellulose ester derivatives. These cellulose ester derivatives possess great potentialiii for various applications, including amorphous solid dispersion, tight junction opening, anionic drug delivery, and gas separation membranes. / MS

Endohedral metallofullerenes (EMF) have attracted increasing attention during past decades for their potential applications in the fields of biomedicine and nanomaterials. Trimetallic nitride template endohedral metallofullerenes (TNT EMFs) are some of the most promising fullerene-based materials (e.g., as MRI and X-ray contrast agents) because of their high yields compared to classic endohedral metallofullerenes. This dissertation addresses the chemical reactivity and regioselectivity of TNT EMFs. Based on the extraordinarily high stability of TNT EMFs relative to empty cage fullerenes and classic endohedral metallofullerenes, macroscopic quantities of high purity TNT EMFs were obtained directly from crude soot in a single facile step by using a cyclopentadiene-functionalized resin to trap the more reactive species via Diels-Alder reactions, allowing the TNT EMFs to pass through. We also developed a support-free chemical separation method of TNT EMFs from Sc- and Lu-based soot extract that makes use of the differing solubilities of unreacted TNT EMFs versus 9-methylanthracene-derivatized empty cage fullerenes. The exohedral functionalization of metallofullerenes can fine-tune their chemical and physical properties. The first N-methylpyrrolidino derivatives of TNT EMFs (Ih Sc3N@C80 and Ih Er3N@C80) were synthesized via 1,3-dipolar cycloaddition of N-methylazomethine ylides (Prato reaction). The demonstration of planar symmetry in the N-methylpyrrolidino derivatives by 13C NMR spectroscopy suggested that the reaction exclusively took place at the 5,6-ring junction. However, both 5,6-ring and 6,6 ring junction adducts were obtained when Ih Sc3N@C80 reacted with N-triphenylmethyl-5-oxazolidinone, as characterized by NMR spectroscopy and X-ray crystallography. The kinetically favored 6,6-ring junction adduct was converted to the thermodynamic product, the 5,6-ring junction adduct, upon thermal equilibration. The synthesis of pyrrolidino derivatives was also extended to two other Sc-based TNT EMFs, D5h Sc3N@C80 and Sc3N@C78. The reactivity and regioselectivity of D5h Sc3N@C80 and Sc3N@C78 were demonstrated by NMR spectroscopy, X-ray crystallography and theoretical calculations. Another type of reaction, the Bingel-Hirsch cyclopropanation was carried out with D3h Sc3N@C78 for the first time, yielding a single Cs-symmetric monoadduct and a dominant C2v-symmetric diadduct for the first time. The symmetric diadduct clearly demonstrates the remarkable regioselectivity control exerted by the encapsulated Sc3N cluster. We employed a LUMO electron density surface computational approach to predict multiadduct docking sites on the ellipsoidal fullerene cage surface. We also successfully synthesized the first derivative of a non-IPR fullerene, the diethyl malonate derivative of Sc3N@C68 by a Bingel-Hirsch reaction. The reactivity and regioselectivity of Sc3N@C68 were investigated by NMR spectroscopy and theoretical calculations. / Ph. D.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第18336号 / 農博第2061号 / 新制||農||1023(附属図書館) / 学位論文||H26||N4843(農学部図書室) / 31194 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 梅澤 俊明, 教授 矢﨑 一史, 教授 三上 文三 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

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