@phdthesis{oai:muroran-it.repo.nii.ac.jp:00010458,
 author = {PERUMALSAMY, Parasuraman and ペルマルサミ, パラスラマン},
 month = {2021-06-23, 2022-03-23},
 note = {application/pdf, 医薬品をはじめとする多くの生物活性化合物は光学活性物質であり, その鏡像異性体は薬と毒のような，互いに異なる生体内作用を示すことが多い。そのため，有効な一方の鏡像異性体を高立体選択的に合成するための不斉合成反応の開発，特に不斉触媒を用いる触媒的不斉合成反応の開発は，新薬やキラル機能性分子を創製するために重要である。その不斉触媒の中で，金属を含有しない有機分子触媒は毒性が無く，空気中で安定であり取り扱いやすく安価であるなどの利点を有するため, 次世代の環境調和型触媒として現在活発な研究開発が行なわれている. 光学活性スピロインダノール類は，抗がん，抗 HIVや抗マラリヤ活性などの多彩な生物活性を示すことから，現在そのスピロインダノール骨格を構築するための有機合成反応の開発が活発に行われている。著者は，その合成反応として触媒的不斉ヘテロ ディールス・アルダー反応に着目し，その反応に有効な有機分子触媒複合系を開発することを目的として本研究を行った。著者は，有機分子触媒複合系として，β—アミノアルコールおよびβ—アミノシリルエーテルをそれぞれ触媒とし，アミノ酸を助触媒とするイサチン類とエノン類との不斉ヘテロ ディールス・アルダー反応を検討した。その結果，触媒としてはその分子中に第１級アミノ基や第１級水酸基，またシロキシ基をもつシンプルなキラルβ—アミノアルコールまたおよびβ—アミノシリルエーテルが，また助触媒としてはアミノ基に保護基したα—アミノ酸が本反応中で複合的に触媒活性機能を発現し，優れた化学収率とジアステレオ選択性およびエナンチオ選択性で目的のキラルイサチン誘導体が得られることが明らかとなった。本研究において著者は，光学活性スピロインダノール類の合成に有効な不斉ヘテロ ディールス・アルダー反応に用いる新規有機分子触媒複合系を開発することに成功した。開発した本触媒系は，他の創薬のために有用な不斉触媒反応においても触媒機能を示すことが期待され，さらに，本反応によって得られる光学活性スピロインダノール類は抗がん作用や他の様々な生物活性化合物の合成中間体としても有用であることから，本研究の成果は, 新薬創製を指向した合成開発研究に大きく貢献できると期待される., Many biologically active compounds, including pharmaceuticals, are optically active and often only one of the enantiomer shows a high biologically activity. Therefore, it is important to develop the synthetic methodology for providing only necessary enantiomer. As the methodology, catalytic asymmetric synthesis, in which the use of a low amount of a chiral catalyst theoretically enables infinite production of optically active compounds, is the most efficient in the synthetic organic chemistry field. Moreover, this methodology is also important in terms of energy saving and environmental friendliness. The chiral catalysts used in catalytic asymmetric syntheses can be divided into two categories of organometallic catalyst and metal-free organocatalyst. Particularly, organocatalyst is stable in air, nontoxic, easy to handle, and inexpensive, so they are being focused on as next-generation, environmentally friendly catalysts. Spirooxindoles are considered to be promising scaffolds in drug discovery. The structure of spirooxindoles is contained in many compounds having pharmacological activities such as contraceptive, anti-HIV, anticancer, antituberculosis, antimalarial, and antiproliferative drugs. Therefore, the development of an effective strategy for the preparation of highly optically pure spirooxindoles is a significantly challenging task in research. The hetero Diels–Alder (HDA) reaction is a versatile tool for effectively forming heterocyclic compounds. Especially, the catalytic asymmetric version of this reaction is the most efficient and convenient method for constructing a chiral heterocyclic skeleton, which acts as a precursor for many biologically active compounds and drugs. In this class of HDA reactions, the reaction of isatins with enones is one of the superior organic transformations for providing unique chiral spirooxindoles containing quaternary chiral carbon center on the structure. Author tried to explore new catalysts component system for this reaction using isatins as diene and enones as dienophile. As a result, author developed simple two catalysts component system consisting of primary β-amino alcohol or γ-amino silyl ether as catalysts and N-protected amino acid as a co-catalyst for the asymmetric HDA reaction of isatins with enones for the first time. These dual component systems showed efficient catalytic activities to afford the chiral spirooxindoles that are efficient synthetic intermediates for many biologically active compounds and drug discovery, in good to excellent chemical yields and with enough stereoselectivities. In this study, author revealed that the new explored catalysts component system showed excellent catalytic activity to the asymmetric HDA reaction of isatins with enones. It is expected that this results should be able to greatly contribute the development of new drugs and its related compounds.},
 school = {室蘭工業大学, Muroran Institute of Technology},
 title = {Development of New Organocatalyst Component System for Asymmetric Hetero Diels–Alder Reaction},
 year = {}
}