The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Professor Kenzo Yamatsugu's research lab specializes in the development of innovative catalytic methods for the synthesis and functionalization of biologically relevant molecules, with a strong focus on carbohydrates and bioactive compounds. The lab pioneers asymmetric synthesis strategies—particularly using earth-abundant metal catalysts and organocatalysts—to construct complex molecular architectures with high stereoselectivity. Key research directions include the catalytic phosphorylation of alcohols, site-selective transformations of polyfunctional sugars, and the design of novel catalysts for protein modification, all aimed at enabling efficient access to pharmaceuticals and functional materials.
Figures are computed from collected data and may differ slightly.
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
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