有機触媒による基質の特定のコンホメーションの認識に基づく不斉反応に関する研究

京都大学0048新制・課程博士博士(工学)甲第20388号工博第4325号新制||工||1670(附属図書館)京都大学大学院工学研究科材料化学専攻(主査)教授 松原 誠二郎, 教授 吉田 潤一, 教授 中尾 佳亮学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDFA

Asymmetric chroman synthesis via an intramolecular oxy-Michael addition by bifunctional organocatalysts.

Cinchona-alkaloid-urea-based bifunctional organocatalysts facilitate the catalytic asymmetric synthesis of chroman derivatives via an intramolecular oxy-Michael addition reaction. Phenol derivatives bearing an easily available (E)-α, β-unsaturated ketone or a thioester moiety are useful substrates for the title transformation. This method represents a facile synthesis of various optically active 2-substituted chromans in high yield

Asymmetric Cycloetherifications by Bifunctional Aminothiourea Catalysts: The Importance of Hydrogen Bonding

Chiral oxacyclic frameworks are prevalent in many natural products and bioactive compounds. In addition, a number of them are important synthetic intermediates. Thus, the synthesis of such structures is a significant goal in the field of organic chemistry. However, the development of catalytic asymmetric cycloetherification for the straightforward synthesis of these compounds remains a challenge. In this study, we propose the use of aminothiourea catalysis as an effective way to accomplish such a challenge. The asymmetric synthesis of chiral oxygen heterocycles, including tetrahydrofurans, tetrahydropyrans, and 1, 3-dioxolanes, is demonstrated herein using intramolecular oxy-Michael addition mediated by bifunctional aminothiourea catalysts

Asymmetric Indoline Synthesis via Intramolecular Aza-Michael Addition Mediated by Bifunctional Organocatalysts

A novel method for the asymmetric synthesis of 2-substituted indolines, employing bifunctional amino(thio)urea catalysts, was developed. The reaction proceeded via an intramolecular aza-Michael addition mediated by activation through hydrogen bonding. The catalytic process was shown to be highly versatile and applicable to a wide range of substrates due to the flexible catalytic mechanism utilizing a noncovalent interaction

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

Bifunctional organocatalysts bearing amino and urea functional groups in a chiral molecular skeleton were applied to the enantioselective synthesis of axially chiral benzamides via aromatic electrophilic bromination. The results demonstrate the versatility of bifunctional organocatalysts for the enantioselective construction of axially chiral compounds. Moderate to good enantioselectivities were afforded with a range of benzamide substrates. Mechanistic investigations were also carried out

Bifunctional Organocatalysts for the Enantioselective Synthesis of Axially Chiral Isoquinoline <i>N</i>‑Oxides

Bifunctional catalysts bearing amino and urea functional groups have been applied for a novel, highly enantioselective synthesis of axially chiral isoquinoline <i>N</i>-oxides, which are promising chiral ligands or organocatalysts in organic synthesis. This is the first example of highly enantioselective synthesis of axially chiral biaryls by bifunctional organocatalysts. Good-to-excellent enantioselectivities were obtained with a range of substrates

Asymmetric Net Cycloaddition for Access to Diverse Substituted 1,5-Benzothiazepines

In this study, the isothiourea-catalyzed enantioselective formal [4+3] cycloaddition of various α,β-unsaturated carboxylic acid derivatives with 2-aminothiophenols was developed. Mechanistic studies suggested that the reaction proceeds via a reversible sulfa-Michael addition to α,β-unsaturated acylammonium intermediates, followed by the enantioselective formation of a seven-membered ring, enabling the facile and divergent synthesis of optically active 2- and 3-substituted 1,5-benzothiazepines. This process was demonstrated to be highly versatile, affording the corresponding products in excellent regioselectivities and high enantioselectivities. Furthermore, this method enabled the synthesis of chiral 2,3-disubstituted 1,5-benzothiazepines in high regio-, enantio-, and diastereoselectivities. Hence, this protocol can be applied for the construction of a library of useful pharmaceutical candidates

Asymmetric Net Cycloaddition for Access to Diverse Substituted 1,5-Benzothiazepines

In this study, the isothiourea-catalyzed enantioselective formal [4+3] cycloaddition of various α,β-unsaturated carboxylic acid derivatives with 2-aminothiophenols was developed. Mechanistic studies suggested that the reaction proceeds via a reversible sulfa-Michael addition to α,β-unsaturated acylammonium intermediates, followed by the enantioselective formation of a seven-membered ring, enabling the facile and divergent synthesis of optically active 2- and 3-substituted 1,5-benzothiazepines. This process was demonstrated to be highly versatile, affording the corresponding products in excellent regioselectivities and high enantioselectivities. Furthermore, this method enabled the synthesis of chiral 2,3-disubstituted 1,5-benzothiazepines in high regio-, enantio-, and diastereoselectivities. Hence, this protocol can be applied for the construction of a library of useful pharmaceutical candidates

Suppression of Ventricular Tachycardia Associated with Cardiac Sarcoidosis by Steroid Therapy

In patients with cardiac sarcoidosis, ventricular tachycardia (VT) is observed in some cases. However, effective therapies for the VT are still unknown. Case: A 50-year old female with cardiac sarcoidosis underwent DDD pacemaker implantation for a high degree atrioventricular block with symptoms of faintness and shortness of breath. One month after the surgery, she was admitted for frequent episodes of non-sustained VT. In the electrophysiologic study (EPS), sustained monomorphic VT and ventricular fibrillation were induced; therefore pacemaker was replaced with implantable cardioverter-defibrillator (ICD). Amiodarone was started orally but it couldn't suppress frequent VT episodes, and frequent ICD shocks were delivered. When the oral steroid therapy was initiated for the cardiac sarcoidosis, it not only suppressed the frequent VT but also improved the atrioventricular nodal dysfunction. In conclusion, steroid therapy might be an option to consider in cardiac sarcoidosis with refractory VT