N - クロロスルホンアミド アルファ - ハロ オキシム ユウドウタイ ノ ハンノウ ニ カンスル ケンキュウ

京都大学0048新制・課程博士博士(工学)甲第10827号工博第2358号新制||工||1306(附属図書館)UT51-2004-G674京都大学大学院工学研究科材料化学専攻(主査)教授 大嶌 幸一郎, 教授 檜山 爲次郎, 教授 吉田 潤一学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDA

A Mild Method for the Synthesis of Carbamate-Protected Guanidines Using the Burgess Reagent

A simple method for the synthesis of carbamate-protected guanidines from primary amines is described. A variety of thioureas derived from primary amines and isothiocyanates react with the Burgess reagent to give the corresponding guanidines via either a stepwise or one-pot procedure. By tuning the carbamoyl units of isothiocyanates and the Burgess reagent, differentially <i>N,N′</i>-diprotected guanidines can be obtained. Selective deprotection of the products affords <i>N-</i>monoprotected guanidines

Development of a manufacturing process toward the convergent synthesis of the COVID-19 antiviral Ensitrelvir

We describe the development of the practical manufacturing of Ensitrelvir, which was discovered as a SARS-CoV-2 antiviral candidate. Scalable synthetic methods of indazole, 1,2,4-triazole and 1,3,5-triazinone structures were established, and convergent couplings of these fragments enabled the development of a concise and efficient scale-up process to Ensitrelvir. In this process, introducing a meta-cresolyl moiety successfully enhanced the stability of intermediates. Compared to the initial route in the medicinal synthetic stage, the overall yield of the longest linear sequence (six steps) was improved by approximately 7-fold. Furthermore, nine out of the twelve isolated intermediates were crystallized directly from each reaction mixture without any extractive work-up (direct isolation). This led to an efficient and environmentally friendly manufacturing process that minimizes waste of organic solvents, reagents, and processing time. This practical process for manufacturing Ensitrelvir should contribute to protection against COVID-19