A5033285773- Asymmetric Synthesis and Catalysis
- Chromatin Remodeling and Cancer
- Mechanisms of cancer metastasis
- Chemical synthesis and alkaloids
- Ocular Oncology and Treatments
- Advanced Synthetic Organic Chemistry
- Synthetic Organic Chemistry Methods
- Cancer Mechanisms and Therapy
- Cyclopropane Reaction Mechanisms
- Sulfur-Based Synthesis Techniques
- Lipoproteins and Cardiovascular Health
- Synthesis of heterocyclic compounds
- Chemical Synthesis and Analysis
- Protein Degradation and Inhibitors
- Catalytic C–H Functionalization Methods
- Synthesis and biological activity
- Lipid metabolism and biosynthesis
- Click Chemistry and Applications
- Fullerene Chemistry and Applications
- Coordination Chemistry and Organometallics
- Synthesis of Organic Compounds
- Pancreatic function and diabetes
- Synthesis and Catalytic Reactions
- Retinal Development and Disorders
- Synthesis and Biological Evaluation
Center for Global Development
2024
Novartis (United States)
2024
Boston Biomedical Research Institute
2019
University of Calgary
1997-2008
Harvard University
2002-2003
University of Delaware
2001-2002
Toyohashi University of Technology
1994
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close Brahma-related gene 1 (BRG1), SMARCA4, are mutually exclusive ATPases the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation expression. No small molecules have been reported that modulate activity via inhibition ATPase activity, an important goal...
[reaction: see text] The stable, crystalline Cr(III)/sulfonamide complex 1a is shown to be an effective catalyst for the Ni/Cr-mediated coupling reaction. A possible mechanism suggested process. also other Cr-mediated reactions. With this catalyst, a concise and efficient synthesis of C14-C26 segment halichondrins has been developed.
Via an X-ray analysis, the sulfonamide bearing R1 = i-Pr, R2 Me, and R3 Me is shown to be a tridentate ligand Cr(III) salt. This class of ligands, represented by t-Bu, 2-naphthyl, effective achieve asymmetric Ni/Cr-mediated coupling reaction and, with C14-C38 segment halichondrins, its synthetic potential has been demonstrated. A possible mechanism suggested for process.
The methyl esters of (l)-phenylalanine and (l)-methionine underwent conjugate additions via their free amino groups to 1-(p-toluenesulfonyl)hexyne, followed by intramolecular acylation the corresponding enamide anions tautomerization afford 2-benzyl-5-n-butyl-3-hydroxy-4-(p-toluenesulfonyl)pyrrole 5-n-butyl-3-hydroxy-2-(2-methylthioethyl)-4-(p-toluenesulfonyl)pyrrole, respectively. a series acyclic cyclic secondary β- γ-chloroamines acetylenic sulfones proceeded similarly under mild...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSilylmethylations of C60 with Grignard Reagents: Selective Synthesis HC60CH2SiMe2Y and C60(CH2SiMe2Y)2 Selection SolventsHideo Nagashima, Hiroshi Terasaki, Eiji Kimura, Katsumasa Nakajima, Kenji ItohCite this: J. Org. Chem. 1994, 59, 6, 1246–1248Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://doi.org/10.1021/jo00085a007RIGHTS & PERMISSIONSArticle...
Abstract In connection with the de elopment of a practical synthesis right half, and its analog E7389, halichondrin B, an efficient scalable two major building blocks is reported. addition, new C20–C26 segment via regiospecific stereoselecti e S N 2' process presented. A sulfonamide class ligands shown to be effective for asymmetric Ni/Cr-mediated reactions under both stoichiometric catalytic conditions, X-ray structure reveals this tridentate. On basis three structures, possible mechanism...
Tertiary acyclic allyl amines and tertiary cyclic alpha-vinyl undergo conjugate additions to acetylenic sulfones produce zwitterion intermediates, followed by 3-aza-Cope rearrangements. In the case of amines, process results in ring-expansion, providing a novel route 9- 17-membered amines. The Hammett plot for reaction 8b with 2a- 2f shows rho = +1.19, which is consistent formation proposed rate-determining step, where electron-withdrawing substituents on arylsulfonyl moiety stabilize...
Advances in the design of permeable peptides and synthesis large arrays macrocyclic with diverse amino acids have evolved on parallel but independent tracks. Less precedent combines their respective attributes, thereby limiting potential to identify peptide ligands for key targets. Herein, we present novel 6-, 7-, 8-mer cyclic (MW 774–1076 g·mol–1) passive permeability oral exposure that feature thioether ring-closing common array formats, including DNA- RNA-templated synthesis. Each herein,...
Abstract Uveal melanoma is a rare and aggressive cancer that originates in the eye. Currently, there are no approved targeted therapies very few effective treatments for this cancer. Although activating mutations G protein alpha subunits, GNAQ GNA11, key genetic drivers of disease, additional drug targets have been identified. Recently, studies identified context-specific roles mammalian SWI/SNF chromatin remodeling complexes (also known as BAF/PBAF) various lineages. Here, we find evidence...
A new synthesis of the naturally occurring (−)-enantiomer dendrobatid alkaloid pumiliotoxin C (1) was achieved by conjugate addition methyl (−)-cis-2-amino-trans-6-methylcyclohexanecarboxylate (3) to 1-(p-toluenesulfonyl)-1-pentyne (4), followed intramolecular acylation afford (4aS,5R,8aR)-4a,5,6,7,8,8a-hexahydro-5-methyl-2-propyl-3-(p-toluenesulfonyl)-4-quinolinone (2). The acetylenic sulfone thus acts as synthetic equivalent an alkene dipole species. required enantiopure amino ester 3...
A novel ring-expansion protocol is based on the conjugate additions of cyclic alpha-vinylamines to (p-toluenesulfonyl)ethyne, followed by aza-Cope rearrangements resulting zwitterions, afford medium and large-ring amines under remarkably mild conditions.
The conjugate additions of β- and γ-chloroamines to acetylenic sulfones afford enamine sulfones, which then undergo intramolecular alkylation produce the corresponding cyclic enamines. This provides a convenient route substituted piperidines, indolizidines, quinolizidines, pyrrolizidines. enantioselective total synthesis alkaloid (−)-indolizidine 167B (also named gephyrotoxin 167B) was thus achieved by cycloaddition (S)-2-(2-chloroethyl)pyrrolidine 1-(p-toluenesulfonyl)-1-pentyne, followed...
Modification of a gut restricted class benzimidazole DGAT1 inhibitor 1 led to 9 with good oral bioavailability. The key structural changes include bioisosteric replacement the amide oxadiazole and α,α-dimethylation carboxylic acid, improving potency permeability. Since is expressed in small intestine, both can suppress postprandial triglycerides during acute lipid challenges rats dogs. Interestingly, only was found be effective suppressing body weight gain relative control diet-induced obese...
ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTUnsymmetrical Ozonolysis of a Diels−Alder Adduct: Practical Preparation Key Intermediate for Heme Total SynthesisDouglass F. Taber and Katsumasa NakajimaView Author Information Department Chemistry Biochemistry, University Delaware, Newark, Delaware 19716 [email protected]Cite this: J. Org. Chem. 2001, 66, 7, 2515–2517Publication Date (Web):March 9, 2001Publication History Received12 December 2000Published online9 March 2001Published inissue 1 April...
Trienes 1 and 3 were obtained in five steps from ethyl 4-acetoxy-3-oxobutanoate 6-iodo-3-methyl-1,3-hexadiene. Intramolecular Diels−Alder cyclization of gave tricyclic lactones 2 4 as the major products, respectively. The key intermediate was converted two to trans-dihydroconfertifolin (5).
Abstract Members of the ATP-dependent SWI/SNF chromatin remodeling complexes are among most frequently mutated genes in cancer, suggesting their dysregulation plays a critical role. The synthetic lethality between catalytic subunits BRM/SMARCA2 and BRG1/SMARCA4 has instigated great interest targeting BRM. Here we have performed in-depth investigation novel dual inhibitors (BRM011 BRM014) BRM BRG1 order to validate utility as chemical probes function, while obtaining insights into therapeutic...
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”
<p>Supplementary Figure S1 shows additional shRNA knockdown data in uveal melanoma cell lines. Supplementary S2 dual BRG1/BRM and BRG1 rescue data. S3 basal SWI/SNF subunit expression, caspase activity viability compound treated lines, mutations cells S4 MITF further RNA-Seq ATAC-Seq set analyses. S5 target gene modulation by treatment lines overexpression S6 genomic location of primers used ChIP-qPCR experiment.</p>
<p>Additional method details for ATAC-Seq Data Analysis and ChIP-qPCR</p>
<p>Supplementary Figure S1 shows additional shRNA knockdown data in uveal melanoma cell lines. Supplementary S2 dual BRG1/BRM and BRG1 rescue data. S3 basal SWI/SNF subunit expression, caspase activity viability compound treated lines, mutations cells S4 MITF further RNA-Seq ATAC-Seq set analyses. S5 target gene modulation by treatment lines overexpression S6 genomic location of primers used ChIP-qPCR experiment.</p>