This work deals with the use of methoxymethyl protecting group in chemistry of cyclodextrins, where this group has not been used very often so far. The work deals with development of optimal methods for introduction and for subsequent removal of the group and shows its usefulness in the preparation of new 6I -O-monosubstituted cyclodextrin derivatives, which are hard to get by standard methods. Key words: cyclodextrin derivatives, methoxymethyl group, protecting group

Carbohydrates play major roles in many biological processes. Therefore, the synthesis of oligosaccharides is of considerable interest for biological, medicinal, and pharmacological studies. Many approaches have been developed for the synthesis of oligosaccharides, in which the main focus is often the formation of the glycosidic bonds. Traditional approaches use protecting group strategies that can be time consuming and can result in poor overall yield. This thesis describes the protecting group-free synthesis of a series of glycosyl donors of a range of mono- and disaccharides. These donors can be used to synthesize unprotected glycosyl chlorides, observed in situ. Reaction of the glycosyl chlorides with a variety of nucleophiles afforded the expected displacement products, giving access to a range of O-, N-, and S-linked glycosides, without resorting to the use of protecting groups.

Carbohydrates play major roles in many biological processes. Therefore, the synthesis of oligosaccharides is of considerable interest for biological, medicinal, and pharmacological studies. Many approaches have been developed for the synthesis of oligosaccharides, in which the main focus is often the formation of the glycosidic bonds. Traditional approaches use protecting group strategies that can be time consuming and can result in poor overall yield. This thesis describes the protecting group-free synthesis of a series of glycosyl donors of a range of mono- and disaccharides. These donors can be used to synthesize unprotected glycosyl chlorides, observed in situ. Reaction of the glycosyl chlorides with a variety of nucleophiles afforded the expected displacement products, giving access to a range of O-, N-, and S-linked glycosides, without resorting to the use of protecting groups.

No description available.

Les héparanes sulfates (HS) sont des polysaccharides linéaires et sulfatés exprimés sur la surface cellulaire où ils interagissent et régulent l’activité de nombreuses proteines, en particulier les cytokines et chimiokines. Ils sont à ce titre de bons candidats médicaments dans des pathologies inflammatoires, autoimmunes ou en oncologie. L’unité répétitive de ce biopolymère est constituée d’un résidu de D-glucosamine lié à un acide uronique par une liaison 1,2-cis. Malheureusement, la formation d’un glycoside 1,2-cis dans la série 2-azido-2-déoxy-D-glucose avec une haute stéréosélectivité reste un des plus grands défis de la glycochimie. Parmi les nombreuses méthodologies permettant d’accéder à la synthèse des fragments d’HS avec de bons rendements et une bonne stéréosélectivité, nous avons été particulièrement intéressés par l’assistance anchimérique d’un groupement protecteur en position 6 du donneur. L’objectif de ce travail était de trouver des groupements protecteurs qui favoriseront la stéréosélectivité 1,2-cis. Nous avons préparés plusieurs donneurs thioglycosides modifiés en position 6 par des différents groupements protecteurs. L’activation des thioglycosides passe par une étape de formation des triflates anomériques. Nous avons élaboré un protocole de suivi de l’activation sur un donneur modèle afin de suivre la formation du triflate anomérique, sa plage de stabilité, ses produits de dégradation ainsi que les produits secondaires d’activation par RMN à basse température. Ensuite, ce protocole d’activation a été utilisé avec tous les donneurs synthétisés afin d’ajuster les conditions de glycosylation. Les tests de glycosylation nous ont permis de décéler plusieurs groupes capables de favoriser la stéréosélectivité 1,2-cis. Certains groupements protecteurs ont manifesté une incompatibilité avec les conditions d’activation des thioglycosides. Pour contourner ce problème, nous avons remplacé les thioglycosides par les donneurs N-phényltrifluoroacétimidates. Après avoir effectué des études d’activation sur ces donneurs toujours par RMN à basse température, les glycosylations ont été effectuées. Finalement, les groupements protecteurs favorisant la stéréosélectivité 1,2-cis ont été testés dans différentes conditions de déprotection afin d’établir la compatibilité de ces groupements protecteurs avec les conditions de synthèse des oligosaccharides d’HS. / Heparin sulfate (HS) are linear and sulfated polysaccharides present at the cell surface. HS interact and regulate activity of numerous proteins, especially cytokines and chemokines. Therefore, HS oligosaccharides are targeted as potential drugs in inflammation, autoimmune disease or tumor treatment. The basic disaccharide unit of HS consists in D-glucosamine residue linked to an uronic acid by 1,2-cis glycosidic linkage. Unfortunately, the formation of highly stereoselective 1,2-cis glycosidic bond in 2-azido-2-deoxy-D-glucose series is still a major concern in glycochemistry. Amongst the numerous methodologies favoring the stereoselective 1,2-cis linkage formation, we were particularly interested in 6-O-anchimeric assistance. Several thioglycoside donors with different protecting groups in position 6 were prepared to find some 1,2-cis stereodirecting protecting groups. Some thioglycoside activation related in literature yields a reactive anomeric triflate intermediate. In order to observe its formation and to determine the limits of its stability and by-product formation, a new low temperature NMR experiment protocol was elaborated. All synthesized donors were tested using this protocol in order to adjust their glycosylation conditions. The glycosylation tests revealed several 1,2-cis stereodirecting protecting groups. Since certain protecting groups were incompatible with thioglycoside activation conditions, corresponding NPTFA donors were used as an alternative. Their activations were monitored by low temperature NMR techniques and followed by their glycosylations. Finally, all 1,2-cis stereodirecting protecting groups were tested in different deprotection conditions to determine the compatibility of chosen protecting groups with our HS oligosaccharide design synthesis.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18232号 / 工博第3824号 / 新制||工||1586(附属図書館) / 31090 / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 杉野目 道紀, 教授 吉田 潤一, 教授 村上 正浩 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

No description available.

The research described herein includes synthesis, spectroscopy, and quantum chemical calculations with focus on the characteristic properties of compounds with bonds between carbon and the heavier Group 14 elements. The chapters based on the first four papers concern σ- and σ/π-conjugated compounds, although the focus of the first paper is on ring strain of bicyclo[1.1.1]pentanes with C, Si, Ge or Sn at the bridgeheads. The relationship between calculated homodesmotic ring strain energies and through-space distances between the bridgehead atoms was evaluated, and it was found that replacing one of the methylene bridges with phospha-methyl gave both low strain and short through-space distance. Two kinds of σ/π-interacting systems were analysed with the difference that the σ- and π-bonded segments were either allowed to rotate freely relative each other or frozen into a conformer with maximal σ/π-interaction. The freely rotating systems are star-shaped oligothiophenes linked by heavy alkane segments. Density functional theory (DFT) calculations of hole reorganization energies support the measured hole mobilites. In summary, longer central oligosilane linkages, when compared to shorter, facilitate intermolecular hole-transfer between oligothiophene units. In 1,4-disilacyclohexa-2,5-dienes, the strength of the π- and pseudo-π interaction depends on the substituents at Si. Vapour phase UV absorption spectroscopy of 2,3,5,6-tetraethyl-1,1,4,4-tetrakis(trimethylsilyl)-1,4-disilacyclohexa-2,5-diene reveals a strong absorption at 273 nm (4.50 eV). Time-dependent DFT calculations further indicate that octastannylated 1,4-disilacyclohexa-2,5-diene has is lowest excited state at 384 nm (3.23 eV). The electronic, geometric and optical properties of substituted 1,4-disilacyclohexa-2,5-dienes were compared with those of the correspondingly substituted siloles. It was found that the lowest excitations of siloles are less tunable than those of 1,4-disilacyclohexa-2,5-dienes. The final section concerns strongly reverse-polarised 2-amino-2-siloxysilenes formed thermally from carbamylpolysilanes, and their lack of reaction with alcohols. Instead, the carbamylsilane reacts with alcohols giving silyl ethers, leading to a new benign route for alcohol protection.