A5084259598- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Microbial Natural Products and Biosynthesis
- Protein Tyrosine Phosphatases
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Synthesis of Organic Compounds
- Bioactive Compounds and Antitumor Agents
- Ubiquitin and proteasome pathways
- Oxidative Organic Chemistry Reactions
- Asymmetric Hydrogenation and Catalysis
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Plant biochemistry and biosynthesis
- Cancer therapeutics and mechanisms
- Helicobacter pylori-related gastroenterology studies
- Cancer Research and Treatments
- Synthesis and Catalytic Reactions
- Phytochemical compounds biological activities
- X-ray Diffraction in Crystallography
- ATP Synthase and ATPases Research
- Enzyme Production and Characterization
- Traditional and Medicinal Uses of Annonaceae
Niigata University
1994-2025
Microbial Chemistry Research Foundation
2015-2024
Laboratoire de Chimie
2024
Chuo University
2020
Graduate School USA
2019
Meiji University
2018
Kanazawa University
2013-2014
Keio University
1990-2012
ETH Zurich
2003-2004
University of Shizuoka
2002
A short and modular synthesis of novel P,N ligands (pinap; see scheme; X=O or NH) is presented. covalently bound chiral group allows the separation atropisomeric diastereomers, thus avoiding resolution involving Pd–amine complexes. The utility demonstrated for three reactions catalyzed by different transition metals; in each case products are obtained with high enantiomeric excess (up to 99 % ee).
Kurz und "bündig": Bei der kurzen modularen Synthese von P,N-Liganden (pinap; siehe Schema, X=O oder NH) ermöglichte eine kovalent gebundene chirale Gruppe die Trennung atropisomeren Diastereomere ohne Einsatz chiraler Pd-Amin-Komplexe. Die neuen Liganden wurden in drei Reaktionen mit unterschiedlichen Übergangsmetall-Katalysatoren getestet; allen Fällen Produkte hohen Enantiomerenüberschüssen erhalten (bis zu 99 % ee). Supporting information for this article is available on the WWW under...
Although growth differentiation factor-5 (GDF5) has been implicated in skeletal development and joint morphogenesis mammals, little is known about its functionality adipogenesis energy homeostasis. Here, we show a critical role of GDF5 regulating brown for systemic expenditure mice. expression was preferentially upregulated adipose tissues from inborn acquired obesity Transgenic overexpression led to lean phenotype reduced susceptibility diet-induced through increased expenditure....
Selective modulation of autophagy is a promising therapeutic strategy, especially for cancer treatment. However, the lack specific inhibitors limits this strategy. The formation ATG12–ATG5–ATG16L1 complex essential targeting ATG12–ATG5 conjugate to proper membranes and generate LC3-II progression autophagy. Thus, ATG5–ATG16L1 protein–protein interactions (PPIs) might inhibit early stage with high specificity. In paper, we report that stapled peptide derived from ATG16L1 exhibits potent...
We describe a simple and convenient synthesis of the western zone caprazamycin B using two catalytic asymmetric reactions as key elements our approach. Desymmetrization 3-methylglutaric anhydride with (S)-Ni(2)-(Schiff base) complex catalyst furnished chiral hemiester, thioamide-aldol reaction mesitylcopper, (R,R)-Ph-BPE, 2,2,5,7,8-pentamethylchromanol β-hydroxy thioamide in good yield enantioselectivity. On further transformation, functionality was converted to corresponding ester. Finally,...
Abstract The abuse of antibacterial drugs imposes a selection pressure on bacteria that has driven the evolution multidrug resistance in many pathogens. Our efforts to discover novel classes antibiotics combat these pathogens resulted discovery amycolamicin (AMM). absolute structure AMM was determined by NMR spectroscopy, X‐ray analysis, chemical degradation, and modification its functional groups. consists trans ‐decalin, tetramic acid, two unusual sugars (amycolose amykitanose),...
Hydrolytic mechanisms of family 18 chitinases from rice (Oryza sativa L.) and Bacillus circulans WL-12 were comparatively studied by a combination HPLC analysis the reaction products theoretical calculation time-courses. All enzymes tested produced beta-anomers chitin hexasaccharide [(GlcNAc)(6)], indicating that they catalyze hydrolysis through retaining mechanism. The hydrolyzed predominantly fourth fifth glycosidic linkages nonreducing end (GlcNAc)(6), whereas B. chitinase A1 second...
We describe the desymmetrization of meso-glutaric anhydrides to chiral hemiesters using a bench-stable homodinuclear Ni2-(Schiff base) complex as catalyst in good excellent yield (up 99%) and enantioselectivity 94%). Using opposite enantiomer catalyst, we obtained same with configuration, thereby gaining access both hemiester enantiomers.
The disruption of the tumor microenvironment (TME) is a promising anti-cancer strategy, but its effective targeting for solid tumors remains unknown. Here, we investigated activity mitochondrial complex I inhibitor intervenolin (ITV), which modulates TME independent energy depletion. By modulating lactate metabolism, ITV induced concomitant acidification intra- and extracellular environment, synergistically suppressed S6K1 in cancer cells through protein phosphatase-2A-mediated...
Two independent formal total syntheses of oseltamivir phosphate were successfully achieved: the first utilized a copper-catalyzed asymmetric three-component reaction strategy, and second l-glutamic acid γ-ester as chiral source to install correct stereochemistry. Both strategies used Dieckmann condensation construct six-membered ring core, after which manipulation functional groups protecting accessed Corey’s intermediate for synthesis phosphate. While was accomplished via four purification...
Catalytic asymmetric total synthesis of caprazol, a lipo-nucleoside antibiotic, has been accomplished employing two the stereoselective C–C bond forming reactions as key transformations. The stereochemistries β-hydroxy-α-aminoester moiety at juncture uridine part and diazepanone part, β-hydroxy-α-amino acid embedded in system, were constructed using diastereoselective isocyanoacetate aldol reaction (dr = 88:12) an enantioselective anti-nitroaldol catalyzed by Nd/Na-chiral amide ligand 12:1,...
Synthesis of the indenotryptoline bisindole alkaloid, BE-54017, was accomplished using osmium-promoted cis-dihydroxylation maleimide as a key step. After optical resolution, absolute configuration this molecule determined by comparing its rotation and HPLC profile to those obtained for BE-54017 derived from enantiopure cladoniamide A, whose stereochemistry has been reported previously. with correct induced apoptosis epidermal growth factor (EGF)-stimulated EGF receptor overexpressing A431...
The direct catalytic asymmetric aldol reaction is an emerging methodology that provides atom-economical access to functionalized chiral building blocks. Thioamides are useful donors due their high-fidelity chemoselective enolization and divergent post-aldol transformations. Herein we describe the incorporation of α-vinyl appendage on a thioamide, which expands utility adducts for natural product synthesis. This vinylated thioamide was not accommodated under previously identified catalyst...
Synthesis of intervenolin, a natural quinolone discovered by screening for selective growth inhibitors cancer cells cocultured with stromal over monocultured cells, was achieved. The synthesis utilized thiocyanate-isothiocyanate rearrangement and Suzuki-Miyaura coupling to furnish the characteristic substituents, iminodithiocarbonate moiety, geranyl side chain, respectively. In vivo studies showed that intervenolin inhibited tumor tissue in model mice.
Four new macrolactones, leptolyngbyolides A-D, were isolated from the cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The planar structures of determined by extensive NMR studies, although complete assignment absolute configuration awaited catalytic asymmetric total synthesis leptolyngbyolide C. took advantage thioamide-aldol reaction using copper(I) complexed with a chiral bidentate phosphine ligand to regulate two key stereochemistries molecule at outset. present demonstrates...
Autophosphorylation of PRR is a critical event for the activation immune signaling in plant. However, detailed function these phosphorylation sites still not well understood. We analyzed an autophosphorylation site Arabidopsis CERK1, Y428, signaling. Biochemical characterization CERK1 mutants transiently expressed N. benthamiana indicated that Y428 plays crucial role vivo differently from previous observation by vitro kinase assay with its cytoplasmic domain. Similar discrepancy between and...
Modulation of prostate stromal cells (PrSCs) within tumor tissues is gaining attention for the treatment solid tumors. Using our original in vitro coculture system, we previously reported that leucinostatin (LCS)-A, a peptide mycotoxin, inhibited cancer DU-145 cell growth through reduction insulin-like factor 1 (IGF-I) expression PrSCs. To further obtain additional bioactive compounds from LCS-A, designed and synthesized series LCS-A derivatives as target Among derivatives, LCS-7 reduced...
[reaction: see text] The enantioselective conjugate addition reaction of Et(2)Zn to Meldrum's acid derived acceptors, mediated by a catalyst formed from Cu(O(2)CCF(3))(2) and phosphoramidite ligand, is reported. Adducts are obtained in useful yields up 94% ee.
The first enantioselective copper-catalyzed conjugate addition of α-substituted benzyl nitriles to alkyl acrylates is described. This protocol allows the direct and 100% atom-economic generation a nitrile-containing quaternary stereogenic center in highly manner. practical application our methodology was demonstrated through concise formal synthesis (−)-aphanorphine.