A5083769463- Chemistry and Chemical Engineering
- Inorganic and Organometallic Chemistry
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Catalytic C–H Functionalization Methods
- Catalytic Alkyne Reactions
- Chemical Synthesis and Analysis
- Veterinary medicine and infectious diseases
- Asymmetric Hydrogenation and Catalysis
- Crystallography and molecular interactions
- Cancer Mechanisms and Therapy
- Bioactive Compounds and Antitumor Agents
- Asymmetric Synthesis and Catalysis
- Mechanisms of cancer metastasis
- Synthesis and Biological Evaluation
- Chromatin Remodeling and Cancer
- Sulfur-Based Synthesis Techniques
- Carbon dioxide utilization in catalysis
- Neuroscience and Neuropharmacology Research
- Pharmaceutical and Antibiotic Environmental Impacts
- Organometallic Complex Synthesis and Catalysis
- Advanced Breast Cancer Therapies
- S100 Proteins and Annexins
- Mycobacterium research and diagnosis
- Microtubule and mitosis dynamics
Yale University
2014-2017
The University of Tokyo
2012
The conversion of terminal alkynes to functionalized products by the direct addition heteroatom-based nucleophiles is an important aim in catalysis. We report design, synthesis, and mechanistic studies half-sandwich ruthenium complex 12, which a highly active catalyst for anti-Markovnikov reductive hydration alkynes. key design element 12 involves tridentate nitrogen-based ligand that contains hemilabile 3-(dimethylamino)propyl substituent. Under neutral conditions, dimethylamino substituent...
The tricyclic diterpene fungal metabolite (+)-pleuromutilin has served as a starting point for antibiotic development. Semisynthetic modification of its glycolic acid subunit at C14 provided the first analogs fit human use, and derivatization C12 led to 12-epi-pleuromutilins with extended-spectrum antibacterial activity, including activity against Gram-negative pathogens. Given inherent limitations semisynthesis, however, accessing derivatives full control over their structure presents an...
Anti-Markovnikov alkyne hydration provides a valuable route to aldehydes. Half-sandwich ruthenium complexes ligated by 5,5'-bis(trifluoromethyl)-2,2'-bipyridine are remarkably active for this transformation. In the presence of 2 mol % metal, wide range functionalized aliphatic and aromatic alkynes hydrated in high yield at ambient temperature.
We describe the development of an enantioselective synthetic route to (+)-pleuromutilin (1), (+)-12-epi-mutilin, and related derivatives. A key hydrindanone was prepared in three steps 48% overall yield from cyclohex-2-en-1-one. 1,4-Hydrocyanation provided a nitrile (53%, or 85% based on recovered starting material) that converted eneimide 57 80% by 1,2-addition methyllithium function, cyclization, situ acylation with di-tert-butyldicarbonate. The employed 2-fold neopentylic coupling...
The half-sandwich ruthenium complexes 1-3 activate terminal alkynes toward anti-Markovnikov hydration and reductive under mild conditions. These reactions are believed to proceed via addition of water metal vinylidene intermediates (4). functionalization propargylic alcohols by pathways is challenging owing decomposition the starting material catalytic intermediates. Here we show that catalyst 2 can be employed convert 1,3-diols in high yield with retention stereochemistry at position....
Target-anchored monovalent degraders are more drug-like than their bivalent counterparts, Proteolysis Targeting Chimeras (PROTACs), while offering greater target specificity control the E3 ligase-anchored degraders, also known as molecular glues. However, discovery has typically been serendipitous, and rules governing identification remain unclear. This study focused on intentional of SMARCA2/A4 using a library based bromodomain-binding ligands. Compound G-6599 emerged lead candidate,...
<title>Abstract</title> Target-anchored monovalent degraders are more drug-like than their bivalent counterparts, Proteolysis Targeting Chimeras (PROTACs), while offering greater target specificity control the E3 ligase-anchored degraders, also known as molecular glues. However, discovery has typically been serendipitous, and rules governing identification remain unclear. This study focused on intentional of SMARCA2/A4 using a library based bromodomain-binding ligands. Compound G-6599...
ADVERTISEMENT RETURN TO ISSUEPREVGreen Chemistry High...Green HighlightsNEXTGreen Articles of Interest to the Pharmaceutical IndustryMelissa A. AshleyMelissa AshleyGenentech Inc., 1 DNA Way, South San Francisco, California 94080, United StatesMore by Melissa Ashley, Miles H. AuklandMiles AuklandChemical Development, Technology & Operations, AstraZeneca, Macclesfield SK10 2NA, U.K.More Aukland, Marian C. Bryan*Marian BryanJanssen R&D, 1400 McKean Road, Spring House, Pennsylvania 19002,...
A general strategy for conjugate addition–C-acylation that enables the synthesis of enantioenriched β-dicarbonyl compounds is described. novel method derivatizing these adducts by stereo- and site-selective zinc-catalyzed addition alkyllithium reagents also reported. These reactions can be performed in tandem to achieve an enantio- diastereoselective four-component coupling. The situ generation weakly basic lithium zincate species central success all three transformations.
Abstract Anti‐Markovnikov alkyne hydration provides a valuable route to aldehydes. Half‐sandwich ruthenium complexes ligated by 5,5′‐bis(trifluoromethyl)‐2,2′‐bipyridine are remarkably active for this transformation. In the presence of 2 mol % metal, wide range functionalized aliphatic and aromatic alkynes hydrated in high yield at ambient temperature.
An improved synthesis of an eneimide, which is a useful precursor to pleuromutilin-based antibiotics, reported. This proceeds in six steps and 17% overall yield (27% based on recovery key hydrindenone intermediate) requires two fewer chromatography five days reaction time than the previously reported route. The use expensive, acutely toxic, precious metal reagents or catalysts has been minimized.
ADVERTISEMENT RETURN TO ISSUEPREVGreen Chemistry High...Green HighlightsNEXTGreen Articles of Interest to the Pharmaceutical IndustryMarian C. Bryan*Marian BryanJanssen R&D, 1400 McKean Road, Spring House, Pennsylvania 19002, United States*Email: [email protected]More by Marian Bryan, Charlotte DaltonCharlotte DaltonCatSci Ltd, CBTC2, Capital Business Park, Cardiff, South Glamorgan CF3 2PX, U.K.More Dalton, Alba Díaz-RodríguezAlba Díaz-RodríguezSynthetic Biochemistry, GSK, Gunnels Wood...
ADVERTISEMENT RETURN TO ISSUEPREVGreen Chemistry High...Green HighlightsNEXTGreen Articles of Interest to the Pharmaceutical IndustryMarian C. Bryan*Marian BryanJanssen R&D, 1400 McKean Road, Spring House, Pennsylvania 19002, United States*Email: [email protected]More by Marian Bryan, Charlotte DaltonCharlotte DaltonCatSci Ltd, CBTC2, Capital Business Park, Cardiff, South Glamorgan CF3 2PX, U.K.More Dalton, Alba Díaz-RodríguezAlba Díaz-RodríguezSynthetic Biochemistry, GSK, Gunnels Wood...
Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and frequently altered in cancer cells, thereby leading to uncontrolled proliferation. In this context, CDK2 has emerged as an appealing target for anticancer drug development. Herein, we describe discovery a series selective small molecule inhibitors beginning with historical compounds from our ERK2 program (e.g., compound 6). Structure-based design led potent tool 32, where excellent selectivity against CDK4 was achieved...
ADVERTISEMENT RETURN TO ISSUEPREVGreen Chemistry High...Green HighlightsNEXTGreen Articles of Interest to the Pharmaceutical IndustryMelissa A. AshleyMelissa AshleyGenentech Inc., 1 DNA Way, South San Francisco, California 94080, United StatesMore by Melissa Ashley, Miles H. AuklandMiles AuklandChemical Development, Technology & Operations, AstraZeneca, Macclesfield SK10 2NA, U.K.More Aukland, Marian C. Bryan*Marian BryanJanssen R&D, 1400 McKean Road, Spring House, Pennsylvania 19002,...
ADVERTISEMENT RETURN TO ISSUEPREVGreen Chemistry High...Green HighlightsNEXTGreen Articles of Interest to the Pharmaceutical IndustryMarian C. Bryan*Marian BryanJohnson & Johnson Limited, 1400 McKean Road, Spring House, Pennsylvania 19002, United States*Email: [email protected]More by Marian Bryan, Charlotte DaltonCharlotte DaltonCatSci Ltd, CBTC2, Capital Business Park, Cardiff, South Glamorgan CF3 2PX, U.K.More Dalton, Louis J. DiorazioLouis DiorazioChemical Development, Technology...
ADVERTISEMENT RETURN TO ISSUEPREVGreen Chemistry High...Green HighlightsNEXTGreen Articles of Interest to the Pharmaceutical IndustryCharlotte DaltonCharlotte DaltonCatSci Ltd, CBTC2, Capital Business Park, Cardiff CF3 2PX, United KingdomMore by Charlotte Dalton, Louis J. DiorazioLouis DiorazioChemical Development, Technology & Operations, AstraZeneca, Macclesfield SK10 2NA, Diorazio, Jaika DoerflerJaika DoerflerAmgen, One Amgen Center Drive, Thousand Oaks, California 91320, StatesMore...
Abstract With the optimal catalyst system RUC/FMBP, many alkyne substrates can be hydrated to form terminal aldehydes.