The University of Tokyo · 생화학·유전·분자생물학
켄조 야마츠구 교수의 연구실은 주로 유기합성화학과 생물학적 분자 합성에 초점을 맞추고 있습니다. 특히 타미플루와 같은 생물활성 물질의 효율적이고 선택적인 합성, 당류의 치밀한 기능화 및 입체선택적 변환, 그리고 단백질의 후성수정을 위한 고기능성 촉매 기반 반응 개발을 핵심 연구 방향으로 삼고 있습니다. 이는 의약품 개발과 생체분자 기반 소재의 설계에 기여하는 기초 연구입니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
In pursuit of a better route: A new catalytic asymmetric synthesis of Tamiflu was developed. The key transformation was an asymmetric Diels–Alder-type reaction of 1 and 2 catalyzed by a barium/F2-FujiCAPO complex in the presence of a CsF co-catalyst to construct the core of Tamiflu (see scheme; TMS=trimethylsilyl). The product was converted into Tamiflu in 11 steps on a gram scale.
Carbohydrates are a fundamental unit playing pivotal roles in all the biological processes. It is thus essential to develop methods for synthesizing, functionalizing, and manipulating carbohydrates for further understanding of their functions and the creation of sugar-based functional materials. It is, however, not trivial to develop such methods, since carbohydrates are densely decorated with polar and similarly reactive hydroxy groups in a stereodefined manner. New approaches to chemo- and sit
Phosphorylation of alcohols is a fundamentally important reaction in both life science and physical science. Product phosphate monoesters play key roles in living organisms, natural products, pharmaceuticals, and organic materials. Most of the chemical methods to date for synthesizing phosphate monoesters, however, require multistep sequences or are limited to specific types of substrates possibly due to harsh conditions. An alternative way to enable the simple production of phosphate monoesters
Auf der Suche nach einem besseren Weg: Bei einer neuen asymmetrischen Synthese von Tamiflu entsteht durch asymmetrische Diels-Alder-Reaktion von 1 und 2 mit einem Barium-(F2-FujiCAPO)-Komplex als Katalysator und CsF als Cokatalysator das Ringsystem (TMS=Trimethylsilyl). Vom Produkt dieses Schritts aus war Tamiflu in 11 Stufen im Gramm-Maßstab zugänglich. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-ed
Members of the genus Mycobacterium cause devastating human diseases, including tuberculosis. Mycobacterium tuberculosis can resist some antibiotics because of its durable and impermeable cell envelope. This barrier is assembled from saccharide building blocks not found in mammals, including galactofuranose (Galf). Within the cell envelope, Galf residues are linked together to afford an essential polysaccharide, termed the galactan. The formation of this polymer is catalyzed by the glycosyltransf
Lysine acylation of proteins is an essential chemical reaction for posttranslational modification and as a means of protein modification in various applications. N,N-Dimethyl-4-aminopyridine (DMAP) derivatives are widely-used catalysts for lysine acylation of proteins; however, the DMAP moiety mostly exists in a protonated, and thus deactivated, form under physiological conditions due to its basicity. An alternative catalytic motif furnishing higher acylation activity would further broaden the p
The elucidation of specific functions of protein kinase C (PKC) subtypes in physiological processes is an important challenge for the future development of new drug targets. Subtype-selective PKC agonists and antagonists are useful biological tools for this purpose. Most of the currently used PKC modulators elicit their activities through binding to the ATP binding site of PKC, which shares many features with other kinases. PKC modulators that target the PKC regulatory domain are considered to b
Antibody-drug conjugates (ADCs) are a major therapeutic tool for the treatment of advanced cancer. Malignant cells in advanced cancer often display multiple genetic mutations and become resistant to monotherapy. Therefore, a therapeutic regimen that simultaneously targets multiple molecules with multiple payloads is desirable. However, the development of ADCs is hampered by issues in biopharmaceutical manufacturing and the complexity of the conjugation process of low-molecular-weight payloads to
Phosphorylated tyrosine is a fundamental building block of bioactive peptides and proteins. However, the chemoselective phosphorylation of tyrosine over other nucleophilic amino acid residues in unprotected peptides remains a significant challenge. Here we report an umpolung strategy that converts the C-terminal tyrosine into an electrophilic spirolactone cyclohexadienone motif through hypervalent iodine oxidation, followed by a 1,2-phospha-Brook rearrangement using phosphite diesters as nucleop
Abstract IR700, a silicon phthalocyanine (SiPc) photosensitizer, is an antibody–drug conjugate payload used clinically. It is, however, the sole SiPc payload to date, possibly due to the difficulty of its synthesis, resulting from its asymmetric phthalocyanine skeleton. Here, we report a new axially substituted SiPc payload that is more easily synthesized. Trastuzumab conjugated with the SiPc showed light- and antigen-dependent cytotoxicity in HER2-overexpressing cancer cell lines.
Abstract Phosphodiesters are important structural motifs observed in a diverse field of molecular science. It is, thus, important to develop a simple and robust way to synthesize them from corresponding alcohols. Here we report a single-step asymmetric phosphodiester synthesis from alcohols with phosphoenolpyruvate phosphodiesters as phosphoryl donors. This transformation allows for the use of various functionalized alcohols as substrates and would be useful for diverse fields including biology
