A5024841565- Synthetic Organic Chemistry Methods
- Microbial Natural Products and Biosynthesis
- Catalytic C–H Functionalization Methods
- Chemical synthesis and alkaloids
- Chemical Synthesis and Analysis
- Alkaloids: synthesis and pharmacology
- Cancer Treatment and Pharmacology
- Chemical Synthesis and Reactions
- Traditional and Medicinal Uses of Annonaceae
- Sulfur-Based Synthesis Techniques
- Radical Photochemical Reactions
- Marine Sponges and Natural Products
- Catalytic Cross-Coupling Reactions
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Oxidative Organic Chemistry Reactions
- Carbohydrate Chemistry and Synthesis
- Synthesis and Catalytic Reactions
- Virus-based gene therapy research
- Coordination Chemistry and Organometallics
- Cancer Cells and Metastasis
- Advanced Synthetic Organic Chemistry
- 14-3-3 protein interactions
- Analytical Chemistry and Chromatography
- Axial and Atropisomeric Chirality Synthesis
Eisai (Japan)
2019-2024
Harvard University
2007-2009
The University of Tokyo
1999-2004
Bunkyo University
1999-2004
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTRadical Cyclization of 2-Alkenylthioanilides: A Novel Synthesis 2,3-Disubstituted IndolesHidetoshi Tokuyama, Tohru Yamashita, Matthew T. Reding, Yosuke Kaburagi, and FukuyamaView Author Information Graduate School Pharmaceutical Sciences The University Tokyo CREST, Japan Science Technology Corporation (JST) 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Cite this: J. Am. Chem. Soc. 1999, 121, 15, 3791–3792Publication Date (Web):April 2,...
An operationally simple and efficient workup method for tetrabutylammonium fluoride (TBAF)-mediated t-butyldimethylsilyl (TBS) deprotection has been developed. The procedure includes addition of a sulfonic acid resin calcium carbonate, followed by filtration evaporation. This eliminates the tedious aqueous-phase extraction process to remove excess TBAF materials derived from TBAF, thereby making protocol highly amenable multiple TBS deprotections. Its efficiency usefulness were demonstrated...
Total synthesis of (−)-strychnine is described. Notable features our include (1) palladium-catalyzed coupling the indole and vinyl epoxide moieties, (2) nine-membered cyclic amine derivative from diol precursor in a one-pot procedure, (3) transannular cyclization amine.
Cr-mediated coupling reactions are usually achieved with a slight excess of given nucleophile. To develop cost-effective use this process, two different approaches have been studied. The first approach depends on consecutive catalytic asymmetric couplings, partners purposely being unbalanced molecular size and complexity. second rests the success in identifying nucleophile, which allows us to achieve satisfactorily 1:1 molar ratio partners. C23−O bond is stereospecifically constructed via...
E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by total synthesis approach through joint research between Kishi group at Harvard University and Eisai. Only 18 months after completion initial milligram-scale synthesis, ten-gram-scale was achieved, providing first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights challenges in developing from synthesis.
Process development of E7130 Drug Substance, which is a novel anticancer drug candidate, described. To accomplish rapid delivery such large and structurally complex substance for first-in-human (FIH) clinical trial, close collaboration among medicinal chemistry, process academia teams was required. The successful establishment suitable synthetic route in concise time frame while negotiating challenging chemical reactions (e.g., asymmetric catalytic Nozaki–Hiyama–Kishi (NHK) reaction...
A convergent total synthesis of leustroducsin B (1), which is known to exhibit a variety biological activities, was successfully carried out. Notable features our include construction the C8 stereocenter by lipase-mediated desymmetrization meso-diol 4 (90.2% ee) and preparation C9−C11 anti-diol moiety addition alkynylzinc reagent 20 aldehyde 19. Furthermore, new diol protecting group, p-silyloxybenzylidene, developed for deprotection from densely functionalized substrates under weakly acidic...
Abstract Despite their outstanding antitumour activity in mice, the limited supply from natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) >10 g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts...
N-Unprotected 2-iodoindoles are synthesized by treatment of 2-stannylindoles with iodine, which in turn prepared tin-mediated radical cyclization 2-alkenylphenylisocyanides. Palladium-catalyzed coupling reactions N-unprotected terminal acetylenes, olefins, carbonylation, and the Suzuki reaction phenyl borate proceed smoothly to furnish corresponding 2,3-disubstituted indoles good excellent yields.
Radical cyclization of o-alkenylthioanilides using hypophosphorous acid and AIBN in the presence Et 3 N proceeded smoothly to furnish corresponding 2,3-disubstituted indoles high yields.Utilizing newly developed condition, a stereocontrolled total synthesis (±)catharanthine has been completed.
The identification of biologically active target compounds and their binding proteins is important in mechanism-of-action studies for drug development. Additionally, the newly discovered provide unforeseen ideas novel discovery subsequent structural transformation to improve specificity. Based on lead final candidate related type 5 phosphodiesterase (PDE5) inhibitor E4021, we designed chemical probes identified by affinity chromatography approach. Aldehyde dehydrogenase family 1 member A3...
<h3>Background</h3> Prostate cancer is the second most common and leading cause of death in men. There are currently limited treatment options for metastatic prostate with poor prognosis, due to immune-cold tumor microenvironment (TME) not responding ICI therapies even high frequency tumor-associated macrophages (TAMs). E7766, as a macrocycle-bridged STING agonist constant activity variants, generates robust anti-tumor immune responses through production proinflammatory cytokines...
Abstract Background and objectives: Natural products have been a rich source of inspiration for drug discovery as demonstrated by the fact that over one-third current therapeutic agents are natural or compounds derived from them. Particularly, when supply product is limited, organic synthesis can offer solution. However, with increasing structural complexity, this approach becomes exponentially more challenging, must meet various requirements, including high overall efficiency, scalability,...
Abstract For see ChemInform in Full Text.
Abstract Background and objectives: Despite the outstanding antitumor activity of halichondrins in mice, limited supply from natural sources has prevented drug development using intact halichondrins. We achieved a total synthesis C52-halichondrin-B amine (E7130) under good manufacturing practice (GMP) conditions. E7130 is not only novel microtubule dynamics inhibitor, but also tumor-microenvironment ameliorator. can increase intratumoral CD31-positive endothelial cells reduce α-SMA-positive...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”