The University of Tokyo · 재료과학
Hiroki Oguri 교수의 연구실은 자연물 합성과 생합성 기반 합성 전략을 융합한 고도화된 유기합성화학을 주요 연구 분야로 삼고 있습니다. 특히 인돌 알칼로이드, 시구아토키신, 테트라하이드로이소퀴닌 알칼로이드 등 복잡한 생물학적 활성을 가진 자연물의 효율적 합성과 생합성 효소를 활용한 다이버전트 합성을 개발하고 있습니다. 금속 촉매를 활용한 고도로 제어된 반응, 특히 니켈 촉매를 통한 삼차 알킬 할라이드의 라디칼성 반응을 통해 매우 높은 공간적 장애를 가진 C(sp³)–C(sp³) 결합을 형성하는 데도 성공하고 있으며, 이는 복잡한 고리 구조를 안정적으로 구축하는 데 기여합니다. 또한, 생물학적 활성 물질의 스크리닝을 위한 고품질 시료 라이브러리 구축을 위한 구조적 다양성을 가진 고리형 스케일드 합성 전략도 개발하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Inspired by the skeletal diversity of naturally occurring indole alkaloids and the rich potential of chemistry developed by Padwa and co-workers, we conceived a pathway entailing six modes of intramolecular reactions leading to indole alkaloid-like skeletons. In this context, an efficient folding pathway via a rhodium-catalyzed tandem cyclization-cycloaddition involving three of the modes has been developed (two of which are shown above) that affords densely functionalized compounds with three d
Ciguatoxins are the major causative toxins of ciguatera seafood poisoning. Limited availability of ciguatoxins has hampered the development of a reliable and specific immunoassay for detecting these toxins in contaminated fish. Monoclonal antibodies (mAbs) specific against both ends of ciguatoxin CTX3C were prepared by immunization of mice with protein conjugates of rationally designed synthetic haptens, 3 and 4, in place of the natural toxin. Haptenic groups that possess a surface area larger t
While metal-promoted activation of tertiary alkyl halides often causes elimination and hydrodehalogenation, we have developed a nickel-catalyzed reductive dimerization that allows the generation of a potently reactive tertiary radical equivalent to form a very congested C(sp(3))-C(sp(3)) bond even below room temperature. The catalytic protocol is applicable to the dimerization of several pyrrolidinoindoline scaffolds through an appropriate choice of catalyst to accommodate different substrate re
To access high-quality small-molecule libraries to screen lead candidates for neglected diseases exemplified by human African trypanosomiasis, we sought to develop a synthetic process that would produce collections of cyclic scaffolds relevant to an assortment of natural products exhibiting desirable biological activities. By extracting the common structural features among several sesquiterpenes, including artemisinin, anthecularin, and transtaganolides, we designed six types of scaffolds with s
Covering: 2000 to 2019Rapid access to genomic data has facilitated the identification of the biosynthetic enzyme genes of alkaloid natural products and elucidation of their biosynthetic pathways. Enzymes for the rapid construction of molecular scaffolds and versatile modifications during the late-stage biosynthesis of complex molecular skeletons constitute unique features of biosynthetic machineries. For example, enzymes involved in an alkaloid biosynthesis. In this review, we discuss three type
The antitumor tetrahydroisoquinoline (THIQ) alkaloids share a common pentacyclic scaffold that is biosynthesized by nonribosomal peptide synthetases involving unique enzymatic Pictet-Spengler cyclizations. Herein we report concise and divergent chemo-enzymatic total syntheses of THIQ alkaloids by merging precise chemical synthesis with in vitro engineered biosynthesis. A recombinant enzyme SfmC responsible for the biosynthesis of saframycin A was adapted for the assembly of these natural product
Copper-catalyzed 6-endo cyclization of N-propargylic β-enaminocarbonyls was developed for the synthesis of oxidation-labile 1,6-dihydropyridines. This synthetic method allows flexible and regio-defined assembly of various substituents at the N1, C2, C3, C4, and C6 positions of 1,6-dihydropyridines under mild conditions.
