Article
Chemistry, Multidisciplinary
Tianze Zhang, Hanmin Huang
Summary: The catalytic C(sp(3))-C(sp(3)) coupling of alkyl halides and tertiary amines offers a promising tool for the rapid decoration of amine skeletons. We developed a metal-free photocatalytic system for the aminomethylation of alkyl halides through radical-involved C(sp(3))-C(sp(3)) bond formation, allowing for the synthesis of sterically congested tertiary amines that are of interest in organic synthesis but not easily prepared by other methods.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Kenji Ota, Kazunori Nagao, Hirohisa Ohmiya
Summary: This method synthesizes sterically hindered alpha-hydroxy carbonyl compounds through radical-radical coupling. It allows for the use of primary, secondary, and tertiary aliphatic carboxylic acids to introduce various alkyl substituents onto ketone moieties of alpha-ketocarbonyls under mild reaction conditions.
Article
Chemistry, Organic
Bin Li, Ruixia Liu, Jing Yang, Jingyuan Luo, Lin Yao, Muqiong Li, Xiaohui Zheng, Ru Jiang, Huifang Nie, Shengyong Zhang
Summary: An efficient enantioselective hydrogenation method using the Ir-Bu-t-ax-Josiphos complex has been developed for the synthesis of chiral bulky tetrahydroisoquinoline analogs with high yields and good to excellent enantioselectivities. This transformation provides a straightforward route to useful derivatives of tetrahydroisoquinolines, which have great potential value in drug molecule and natural product research.
Article
Chemistry, Multidisciplinary
Hyo-Jun Lee, Xiao Huang, Shigeyoshi Sakaki, Keiji Maruoka
Summary: A new bio-inspired approach for amide and peptide synthesis using a-amino esters with a potential activating group (PAG) at the ester residue is reported. The ester functionality is activated under mild metal-free conditions by exploiting the dearomatization of phenols with hypervalent iodine(III) reagents. Highly reactive acyl fluoride intermediates are successfully generated using a pyridine hydrogen fluoride complex, facilitating the smooth formation of sterically hindered amides and peptides from bulky amines and a-amino esters.
Article
Chemistry, Organic
Min Tao, Jiasheng Qian, Zuanguang Chen, Lin-Kun An, David M. Wilson, Jianbo Liu
Summary: We report the one-pot synthesis of N-CF3 heteroaryl amides from heteroaryl carboxylic acids and sterically hindered isothiocyanates, including various amino acid analogues, in the presence of AgF. This method represents a complementary approach to our previous work and allows modification of previously inaccessible structures, including alpha-tertiary amines and N-CF3-modified pharmaceuticals.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Optics
Mikhail A. Panfilov, Tatyana Yu. Karogodina, Yao Songyin, Oleg Yu. Karmatskih, Alexey Yu. Vorob'ev, Irina S. Tretyakova, Evgeni M. Glebov, Alexander E. Moskalensky
Summary: This paper extends the library of possible modifications of BODIPYs by presenting experimental data and quantum chemical calculations for a new family of meso-substituted BODIPYs with nitrophenyl groups. The optical properties of the novel compounds are characterized and it is shown that the fluorescence quantum yield and singlet oxygen generation efficiency vary significantly within the family. The experimental data presented in this paper may be useful for further designing of BODIPY dyes and NO photodonors.
JOURNAL OF LUMINESCENCE
(2022)
Review
Chemistry, Multidisciplinary
Max Lubberink, William Finnigan, Sabine L. Flitsch
Summary: Amide bonds are commonly formed in the pharmaceutical industry and there is a growing interest in biocatalytic methods for their synthesis. The use of low water systems and ATP-dependent enzymes have shown promise in driving amide bond formation. A publicly available database, RetroBioCat, has been compiled to provide literature on these methods.
Article
Chemistry, Inorganic & Nuclear
William R. Kerr, Marie A. Squire, Christopher M. Fitchett
Summary: In this study, enantiomerically pure chelating NHC-isobornylamide was synthesized and reacted with palladium and platinum salts. The results showed that the steric bulk of the chiral group played an important role in the interaction with the metal atom, and the complexes formed with acetylacetonate ligands exhibited E/Z isomerism.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Hao Liu, Wei Chi, Lin Dong
Summary: A novel C-H acyloxylation method using peresters as reagents and [Ru(p-cymene)Cl2]2 as catalyst has been developed. By combining ruthenium(II) with AgBF4, CoI2, and 2,2,6,6-tetramethyl-1-piperidinyloxy, various biaryl compounds can be obtained in satisfactory yields within minutes. The reactivity of the reaction is strongly influenced by steric hindrance.
JOURNAL OF PHYSICAL CHEMISTRY C
(2023)
Article
Chemistry, Organic
Jason P. Hibbard, Jessalyn G. Yam, Eyad B. Alsalek, Ana Bahamonde
Summary: A mild sustainable protocol has been developed to couple primary alkyl chlorides and bromides with amides, allowing access to a remarkably orthogonal scope without the need for strongly basic conditions, high temperatures, or organometallic catalysts. K3PO4 is used to facilitate the formation of secondary and tertiary amides, with alkylated amide products obtained in good to excellent yields, showing no substantial limitations based on the steric and electronic properties of the coupling partners.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Aaron S. Crossman, Jake X. Shi, Sebastian M. Krajewski, Laura A. Maurer, Michael P. Marshak
Summary: The synthesis and reactivity of 2,6-dimesitylbenzoyl triflate (1) is described, along with methods for cleaving C-O bonds in ethers, generating alkyl triflates in situ, and introducing m-terphenyl groups via flexible alkoxy linkers to nucleophiles of interest. The advantages and limitations of cyclic ether polymerizations are discussed, as well as the preparation and characterization of acylammonium reaction intermediates. Additionally, an intramolecular FriedelCrafts acylation and XRD characterization of six compounds are detailed.
Review
Chemistry, Multidisciplinary
Shyam Basak, Laura Winfrey, Betty A. Kustiana, Rebecca L. Melen, Louis C. Morrill, Alexander P. Pulis
Summary: Boranes have the ability to mediate hydride abstraction from amino C-H bonds, resulting in the generation of reactive iminium hydridoborate salts that can participate in various stoichiometric and catalytic processes. These reactions include manipulation of amino scaffolds and the use of amine-based reagents for reactions such as transfer hydrogenation and alkylation.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Xiaoling Wang, Jing Li, Yujiro Hayashi
Summary: Peptides and proteins receive significant attention in academia and industry, and the introduction of unusual amino acids allows for the modification of their properties. However, research on peptides with sterically hindered peptide bonds is limited due to the lack of an efficient synthetic approach.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Shan Shan Ng, Zicong Chen, On Ying Yuen, Chau Ming So
Summary: A novel family of phosphine ligands was designed and synthesized, which showed excellent catalytic efficiency in the synthesis of triortho-substituted biaryls. The coordination mode of the ligand with palladium was confirmed by single-crystal X-ray crystallography.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Applied
Sofia Strekalova, Alexander Kononov, Vladimir Morozov, Olga Babaeva, Elena Gavrilova, Yulia Budnikova
Summary: This study describes the electrochemical amidation of C(sp2)-H and C(sp3)-H bonds of a wide range of arenes using nitriles as amide sources, achieved under mild conditions without the need for metal catalysts or external oxidizing agents. The method offers moderate to high yields, can be applied to arenes with diverse functional groups, and is suitable for gram scale synthesis. The key role of the hydroxyl radical as an inductor generated during the oxidation of water has been established through EPR experiments.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Athanasios Papangelis, Trond Ulven
Summary: The study presents a highly selective method for synthesizing LPC and mixed PC without the need for chromatography. By synthesizing an intermediate and using TFA in aqueous solution to remove the protecting group, the synthesis of pure LPC was achieved.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biology
Natasja Barki, Daniele Bolognini, Ulf Borjesson, Laura Jenkins, John Riddell, David Hughes, Trond Ulven, Brian D. Hudson, Elisabeth Rexen Ulven, Niek Dekker, Andrew B. Tobin, Graeme Milligan
Summary: Volatile small molecules, including SCFAs, can act on the body in a hormone-like manner through specific GPCRs. FFA2 and FFA3 are the primary GPCR targets for SCFAs. They have distinct functions and regulate cellular activity and calcium levels through different mechanisms and signaling pathways in the gut and nervous system.
Article
Biochemistry & Molecular Biology
Chiara Morozzi, Max Sauerland, Luke F. Gamon, Asmita Manandhar, Trond Ulven, Michael J. Davies
Summary: This study introduces a novel method to visualize, isolate, enrich, and characterize cellular targets of alpha,beta-unsaturated carbonyls by introducing an alkyne tag. Using this approach, it is shown that dimethylfumarate forms adducts with multiple intracellular targets, including GAPDH.
Article
Biochemistry & Molecular Biology
Max B. Sauerland, Christina Helm, Lasse G. Lorentzen, Asmita Manandhar, Trond Ulven, Luke F. Gamon, Michael J. Davies
Summary: Alpha, beta-unsaturated carbonyls are commonly found in environmental toxins and therapeutic drugs. However, the specific targets and mechanisms of these compounds are poorly understood. Recently, a click-chemistry method has been developed to visualize and enrich adducted proteins for further characterization. LC-MS proteomic analysis has identified the cellular targets of DMFU and MMFU.
Article
Pharmacology & Pharmacy
Yufang Deng, Claudia V. Perez Almeria, Lieke van Gijzel, Kay Schaller, Line Vedel, David E. Gloriam, Trond Ulven, Hans Brauner-Osborne
Summary: This study systematically investigated the structure-activity relationship of GPR15L(71-81) using truncations/extensions, alanine-scanning, and N- and C-terminal capping. The results showed that the C-terminal alpha carboxyl group and the residues Leu(78), Pro(75), Val(74), and Trp(72) are critical for receptor interaction and contribute significantly to the peptide potency. Additionally, the study also identified the importance of Lys192 and Glu272 residues in GPR15 for the potency of the GPR15L peptide.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Endocrinology & Metabolism
Estela Lorza-Gil, Gabriele Kaiser, Christopher Carlein, Markus D. A. Hoffmann, Gabriele M. Koenig, Sieglinde Haug, Leticia Prates Roma, Elisabeth Rexen Ulven, Trond Ulven, Evi Kostenis, Andreas L. Birkenfeld, Hans-Ulrich Haering, Susanne Ullrich, Felicia Gerst
Summary: Research shows that NEFA plays an important role in the functional maturation and adaptive insulin secretion of neonatal beta cells, with FFA1 being a critical factor. FFA1 promotes insulin secretion and is essential in the adaptation of offspring beta cells to parental high-fat feeding.
Article
Chemistry, Medicinal
Marija Ciba, Bethany Dibnah, Brian D. Hudson, Elisabeth Rexen Ulven
Summary: The succinate receptor (SUCNR1) has emerged as a potential target for the treatment of metabolic and inflammatory diseases. This study developed the first potent fluorescent tool compounds for SUCNR1 and identified key differences in ligand binding between human and mouse SUCNR1.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Alice Valentini, Katrine Schultz-Knudsen, Anders Hojgaard Hansen, Argyro Tsakoumagkou, Laura Jenkins, Henriette B. Christensen, Asmita Manandhar, Graeme Milligan, Trond Ulven, Elisabeth Rexen Ulven
Summary: This study reports the discovery of the first high potency FFA2 antagonists through bioisosteric replacement of the carboxylic acid group of CATPB and SAR investigations. The preferred compound TUG 2304 exhibited IC50 values of 3-4 nM in cAMP and GTP gamma S assays, favorable physicochemical and pharmacokinetic properties, and the ability to completely inhibit propionate induced neutrophil migration and respiratory burst.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Viktoria M. S. Kjaer, Viktorija Daugvilaite, Tomasz M. Stepniewski, Christian M. Madsen, Astrid S. Jorgensen, Kaustubh R. Bhuskute, Asuka Inoue, Trond Ulven, Tau Benned-Jensen, Siv A. Hjorth, Gertrud M. Hjorto, Ee Von Moo, Jana Selent, Mette M. Rosenkilde
Summary: The chemotactic receptor GPR183 and its ligand 7 alpha,25-OHC play important roles in immune cell positioning. The internalization of GPR183 is influenced by the C terminus, β-arrestin, caveolin, and dynamin. β-arrestin enhances ligand-induced internalization of GPR183, but it is not required. Internalization and chemotaxis are regulated by distinct mechanisms involving G protein activation and β-arrestin-mediated desensitization. These findings have implications for the development of GPR183-targeting drugs for specific diseases.
Article
Chemistry, Medicinal
Ruwei Yao, Anders A. A. Jensen, Hogan P. P. Bryce-Rogers, Katrine Schultz-Knudsen, Libin Zhou, Nicklas P. P. Hovendal, Henrik Pedersen, Mariusz Kubus, Trond Ulven, Luca Laraia
Summary: The recombination of natural product fragments is an important strategy for discovering bioactive compounds. We synthesized a compound library enriched in spirocyclic ring fusions using alkaloid-inspired scaffolds. The library exhibited excellent drug-like properties and targeted screening led to the identification of hits with significant agonist or antagonist activity against specific serotonin and dopamine receptors. Optimization of one of these hits resulted in a promising lead compound with high selectivity as a dual 5-HT2B/C antagonist.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Dmitrii Kalinin, Trond Ulven
Summary: A chemoselective Pd-mediated carbonylative Negishi-type catalytic protocol for the synthesis of (hetero)-aryl ketones is described. The protocol utilizes the PEPPSI-IPr precatalyst and CO gas at atmospheric pressure to facilitate the carbonylative coupling between various C-(sp3)-hybridized organozinc reagents and a wide range of aryl iodides, including substrates with aldehyde, aniline, phenol, or carboxylic acid groups, and heteroaryls.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Viktoria Madeline Skovgaard Kjaer, Tomasz Maciej Stepniewski, Brian Medel-Lacruz, Lisa Reinmuth, Marija Ciba, Elisabeth Rexen Ulven, Massimiliano Bonomi, Jana Selent, Mette Marie Rosenkilde
Summary: The G protein-coupled receptor GPR183 uses two ligand entry channels to recognize chemically diverse ligands. The study reveals the ligand binding pathway of GPR183 and its importance in understanding the receptor's functionality and ligand recognition.
Meeting Abstract
Endocrinology & Metabolism
F. Gerst, E. Lorza-Gil, G. Kaiser, T. Ulven, E. Kostenis, H. -U. Haring, A. L. Birkenfeld, S. Ullrich
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
