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  • 02월 20일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제113회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Privileged Substructure-Based Diversity-Oriented Synthesis Pathway for Diverse Pyrimidine-Embedded Polyheterocycles

2014년 2월 19일 10시 53분 21초
ORGN.P-811 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
4월 16일 (수요일) 16:00~19:00
저자 및
김희준, 박승범*
서울대학교 화학부, Korea

Facile fabrication of a structurally diverse small-molecule library plays a crucial role in drug discovery and chemical biology. In particular, the unbiased collection of small molecules has become an inevitable resource because it can provide a unique opportunity for the identification of novel chemical entities from phenotype-based screening, which is the leading approach for the development of first-in-class drugs. Diversity-oriented synthesis (DOS) plays an indispensable role to access the unexplored molecular frameworks with maximum structural and stereo-chemical diversity. Along with this endeavor, we proposed a privileged substructure-based DOS (pDOS) for the efficient generation of distinct polyheterocyclic core skeletons embedded with privileged substructures. Pyrimidine has been extensively explored in synthetic and medicinal chemistry owing to its unique mimicking of nucleosides and hydrogen bonding ability with nucleic acids in biological systems. We have developed a new pDOS strategy with pyrimidine as the privileged substructure. Five core skeletons were synthesized by silver- or iodine-mediated cascade cyclization with various amines under different reaction conditions. The resulting discrete scaffolds consist of unique pyrimidine-embedded polyheterocycles fused with different ring sizes and orientation. The molecular diversity of each scaffold was successfully confirmed by a structural alignment of energy-minimized 3D conformers, shape diversity studies using PMI analysis, and PCA analysis. This pDOS strategy allows the fabrication of unique polyheterocycles along with a wide spatial coverage around pyrimidine as the privileged substructure that ensures high potential for molecular interactions with biopolymers in a selective and specific manner.