- Crystal structure, thermal, luminescent and terahertz time domain spectroscopy of magnesium N-phthaloyl-β-alaninate: A combined experimental and theoretical study
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A magnesium complex using N-phthaloyl-β-alanine (NPA) as ligand was synthesized and its crystal structure was characterized by single-crystal X-ray diffraction analysis. The Fourier transformation infrared spectroscopy (FTIR), thermogravimetry (TG) and differential thermal analysis (DTA), fluorescence spectroscopy and terahertz time-domain spectroscopy (THz-TDS) were performed for magnesium N-phthaloyl-β-alaninate (MgNPA). The coordination geometry around Mg (II) has found to be distorted octahedral and the coordination mode of NPA in MgNPA is monodentate i.e. η1μ1. The significant enhancement was observed in the emission intensity of MgNPA complex as compared to the ligand NPA during solid state photoluminescence spectroscopy. The computational investigations of the complex were carried out at B3LYP/6-31 + G (d,p) level in gas phase to support our experimental results. The small energy gap between frontier molecular orbitals (FMOs) manifested that MgNPA is a very reactive, chemically soft and optically active complex. The terahertz time domain spectroscopy of the complex and ligand was performed in order to characterize as well as to find out refractive index and absorption coefficient in 0.2–3.2 THz frequency range. Both the complex and ligand shows the characteristic absorption peaks in this frequency range. The decrease in refractive index is observed by the complexation of NPA with Mg.
- Nadeem, Muhammad,Bhatti, Moazzam H.,Sayin, Koray,Yunus, Uzma,Mehmood, Mazhar,Mehboob, Shoaib,Fl?rke, Ulrich
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Read Online
- Synthesis and characterization of unique new lithium, sodium and potassium coordination polymers
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Five new alkali metal coordination compounds [Li(NPG)](1a), [Na(NPG)2]?2H2O(2a), [C8H5KO4](3a), [Li(NPA)2H2O](1b) and [Na(NPA)2](2b) wherein (NPG = N-phthaloyl glycine, NPA = N-phthaloyl-?-alanine) have been synthesized and characterized by means of X ray single crystal analysis, Infrared spectroscopy (IR), Thermogravimetric analysis (TGA) and Florescence spectroscopy. The compounds 1a, 2a, 3a and 2b showed metal directed self-assembly supramolecular network structures. The crystal structure of compounds 1a and 1b showed distorted tetrahedral geometry with coordination number 4 around lithium. The carboxylate coordination modes were η2μ3and η1μ1 in 1a and 1b respectively. The compounds 2a and 2b exhibited distorted octahedral geometry with coordination number 6 around sodium. The carboxylate coordination mode in 2a and 2b is η2μ2. The objective was to synthesize potassium complex [K(NPG)], but N-phthaloyl glycine was hydrolysed due to exothermic reaction in the presence of strong base, resulted, the formation of 3a. The multiple coordination modes of alkali metal ions to the carboxylate and ring carbonyl oxygen atoms of NPG and NPA produced unique three dimensional architectures. The compounds 1b and 2b showed two strong fluorescence emissions enhancement (blue emission maxima) with greater intensity comparative to NPA, while the compounds 1a and 2a showed two weak fluorescence emissions with less intensity comparative to ligand (NPG). The base hydrolysis of NPG with in the compound 3a resulted the change of ligand based fluorochrome, which produced different shape emission spectrum as compared to other compounds.
- Nadeem, Muhammad,Bhatti, Moazzam H.,Yunus, Uzma,Mehmood, Mazhar,Asif, Hafiz Muhammad,Mehboob, Shoaib,Fl?rke, Ulrich
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Read Online
- Thiamin Biosynthesis in Yeast. Origin of the Five-Carbon Unit of the Thiazole Moiety
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Radioactivity from D--, D--, and D-glucose, from D-fructose, and from glycerol is incorporated nonrandomly into the C5 chain of the thiazole moiety of thiamin in Saccharomyces cerevisiae.The incorporation pattern leads to inference that the C5 chain is derived from a 2-pentulose, which is generated from the hexose precursors by the oxidative as well as by the nonoxidative pentose phosphate pathway.A chemically rational scheme for the biogenesis of the thiazole moiety of thiamin is presented.
- White, Robert L.,Spenser, Ian D.
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Read Online
- Convergent Route to β-Amino Acids and to β-Heteroarylethylamines: An Unexpected Vinylation Reaction
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Various protected β2-amino acids can be prepared by radical addition of β-phthalimido-α-xanthyl propionic acid, both as the free acid or as the ethyl ester. Successive radical additions provide access to more complex structures. In the case of the free acid, addition to certain heteroaromatics leads directly to β-heteroarylethylamines through spontaneous decarboxylation of the intermediate adduct. Forcing the decarboxylation in some cases generated a vinyl group by decarboxylative elimination of the phthalimido group.
- Chen, Xuan,Zard, Samir Z.
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supporting information
(2020/05/05)
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- Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
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Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.
- Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
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p. 6949 - 6957
(2020/10/02)
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- Synthesis, anti-mycobacterial and cytotoxic evaluation of substituted isoindoline-1,3-dione-4-aminoquinolines coupled: Via alkyl/amide linkers
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A series of secondary amine-substituted isoindoline-1,3-dione-4-aminoquinolines were prepared via microwave heating and assayed for their anti-mycobacterial activities. The compound with a butyl chain as a spacer between the two pharmacophores and piperidine as the secondary amine component on the isoindoline ring was the most potent and non-cytotoxic among the synthesized compounds, exhibiting a minimum inhibitory concentration (MIC99) of 6.25 μg mL-1 against Mycobacterium tuberculosis.
- Rani, Anu,Viljoen, Albertus,Johansen, Matt D.,Kremer, Laurent,Kumar, Vipan
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supporting information
p. 8515 - 8528
(2019/03/21)
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- Substituted 1,3-dioxoisoindoline-4-aminoquinolines coupled via amide linkers: Synthesis, antiplasmodial and cytotoxic evaluation
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Synthesis of C-5-substituted 1,3-dioxoisoindoline-4-aminoquinolines having amide group as a spacer was developed with an intent to evaluate their antiplasmodial activities. The synthesized dioxoisoindoline-aminoquinolines tethered with β-alanine as a spacer and secondary amine as substituent displayed good anti-plasmodial activities. Compound 7j, with an optimum combination of β-alanine and an ethyl chain length as linker along with diethylamine as the secondary amine counterpart at dioxoisoindoline proved to be most potent and non-cytotoxic with IC50 of 0.097 μM against W2 strain of P. falciparum and a selective index of >2000.
- Rani, Anu,Legac, Jenny,Rosenthal, Philip J.,Kumar, Vipan
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- Regioselective β-Csp3-Arylation of β-Alanine: An Approach for the Exclusive Synthesis of Diverse β-Aryl-β-amino Acids
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An approach for the synthesis of a variety of new β-aryl-β-amino acids has been developed via a palladium-catalyzed auxiliary-directed regioselective Csp3-H arylation of the unactivated β-methylene bond of β-alanine. The use of 8-aminoquinoline amide as an auxiliary efficiently directs the desired regioselective β-Csp3-H functionalization. The developed protocol enables the easy and straightforward access to several high-value β-aryl-β-amino acids useful for peptide engineering, starting from inexpensive and readily available β-alanine precursors in moderate to excellent yields.
- Chowdhury, Sushobhan,Vaishnav, Roopal,Panwar, Namita,Haq, Wahajul
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p. 2512 - 2522
(2019/03/07)
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- Rh(III)-Catalyzed C-H Amidation of Arenes with N-Methoxyamide as an Amidating Reagent
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The Rh(III)-catalyzed amidation of C(sp2)-H bonds has been reported by employing the N-methoxyamide as a novel amino source. An excellent level of functional group tolerance can be achieved when N-methoxyamide derivatives are used as the amidating reagents. Importantly, several known bioactive compounds such as Aminalon, Pregabalin, Gabapentin, and Probenecid can be transformed to effective amidating reagents, as a way to facilitate the development of new bioactive molecules.
- Ju, Guodong,Li, Guobao,Qian, Guanwen,Zhang, Jingyu,Zhao, Yingsheng
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supporting information
p. 7333 - 7336
(2019/10/08)
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- MODULATORS OF G-PROTEIN COUPLED RECEPTORS
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This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize or partially agonize or antagonize) glucagon?like peptide?1 receptor ("GLP?1R") and/or the gastric inhibitory polypeptide receptor ("GIPR"). The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which modulation (e.g., agonism, partial agonism or antagonism) of GLP?1R and/or GIPR activities is benficial for the treatment or prevention of the underlying pathology and/or symptoms and/or progression of the disease, disorder, or condition. In some embodiments, the modulation results in an enhancment of (e.g., an increase in) existing levels (e.g., normal or below normal levels) of GLP?1R and/or GIPR activity (e.g., signaling). In some embodiments, the chemical entities described herein further modulate (e.g., attenuate, uncouple) -arrestin signaling relative to what is observed with the native ligand. This disclosure also features compositions as well as other methods of using and making the said chemical entities.
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Page/Page column 177-178
(2019/10/15)
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- A Direct Approach to Decoration of Bioactive Compounds via C-H Amination Reaction
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The development of new methods to achieve the direct synthesis of bioactive organic molecules is always an important topic in organic synthesis. We hereby demonstrate that N-methoxyamide is an excellent amino source in the iridium-catalyzed intermolecular C-H amination reaction. The linkage of two bioactive organic molecules can be well achieved with this new protocol. More than 20 examples of decorated bioactive compounds were reported, which can facilitate the discovery of new bioactive molecules.
- Ju, Guodong,Yuan, Chunchen,Wang, Dongjie,Zhang, Jingyu,Zhao, Yingsheng
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p. 9852 - 9855
(2019/12/24)
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- Synthesis of Carboxylic Acids by Palladium-Catalyzed Hydroxycarbonylation
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The synthesis of carboxylic acids is of fundamental importance in the chemical industry and the corresponding products find numerous applications for polymers, cosmetics, pharmaceuticals, agrochemicals, and other manufactured chemicals. Although hydroxycarbonylations of olefins have been known for more than 60 years, currently known catalyst systems for this transformation do not fulfill industrial requirements, for example, stability. Presented herein for the first time is an aqueous-phase protocol that allows conversion of various olefins, including sterically hindered and demanding tetra-, tri-, and 1,1-disubstituted systems, as well as terminal alkenes, into the corresponding carboxylic acids in excellent yields. The outstanding stability of the catalyst system (26 recycling runs in 32 days without measurable loss of activity), is showcased in the preparation of an industrially relevant fatty acid. Key-to-success is the use of a built-in-base ligand under acidic aqueous conditions. This catalytic system is expected to provide a basis for new cost-competitive processes for the industrial production of carboxylic acids.
- Sang, Rui,Kucmierczyk, Peter,Dühren, Ricarda,Razzaq, Rauf,Dong, Kaiwu,Liu, Jie,Franke, Robert,Jackstell, Ralf,Beller, Matthias
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supporting information
p. 14365 - 14373
(2019/09/06)
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- Organocatalyzed Aerobic Oxidation of Aldehydes to Acids
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The first example organocatalyzed aerobic oxidation of aldehydes to carboxylic acids in both organic solvent and water under mild conditions is developed. As low as 5 mol % N-hydroxyphthalimide was used as the organocatalyst, and molecular O2 was used as the sole oxidant. No transition metals or hazardous oxidants or cocatalysts were involved. A wide range of carboxylic acids bearing diverse functional groups were obtained from aldehydes, even from alcohols, in high yields.
- Dai, Peng-Fei,Qu, Jian-Ping,Kang, Yan-Biao
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supporting information
p. 1393 - 1396
(2019/02/26)
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- Synthesis method of cosmetic dipeptide
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The invention discloses a synthesis method of cosmetic dipeptide and belongs to the technical field of polypeptide synthesis. The synthesis method comprises the following steps: protecting alanine byphthalic anhydride to prepare phthaloyl-protected alanine; then reacting with an acyl chlorination reagent to generate a corresponding acyl chloride product; enabling histamine and hexamethyldisilazane to react to obtain a silane protection object of histamine; then reacting with the acyl chloride product to obtain phthaloyl-protected dipeptide; finally, carrying out deprotection under a specificcondition to obtain the cosmetic dipeptide, wherein the cosmetic dipeptide is decarboxycarnosine. The synthesis method provided by the invention does not utilize a condensing agent and has the advantages of cheap and easy-to-obtain raw materials, few byproducts and high yield (the total yield is 78.6 to 86.4 percent); the dipeptide with high purity (the purity is higher than 99 percent) is easy toobtain; the cost is reduced and the synthesis method is suitable for large-batch production.
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Paragraph 0029; 0034
(2019/01/10)
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- ω-Phthalimidoalkyl Aryl Ureas as Potent and Selective Inhibitors of Cholesterol Esterase
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Cholesterol esterase (CEase), a serine hydrolase thought to be involved in atherogenesis and thus coronary heart disease, is considered as a target for inhibitor development. We investigated recombinant human and murine CEases with a new fluorometric assay in a structure–activity relationship study of a small library of ω-phthalimidoalkyl aryl ureas. The urea motif with an attached 3,5-bis(trifluoromethyl)phenyl group and the aromatic character of the ω-phthalimide residue were most important for inhibitory activity. In addition, an alkyl chain composed of three or four methylene groups, connecting the urea and phthalimide moieties, was found to be an optimal spacer for inhibitors. The so-optimized compounds 2 [1-(3,5-bis(trifluoromethyl)phenyl)-3-(3-(1,3-dioxoisoindolin-2-yl)propyl)urea] and 21 [1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-(1,3-dioxoisoindolin-2-yl)butyl)urea] exhibited dissociation constants (Ki) of 1–19 μm on the two CEases and showed either a competitive (2 on the human enzyme and 21 on the murine enzyme) or a noncompetitive mode of inhibition. Two related serine hydrolases—monoacylglycerol lipase and fatty acid amide hydrolase—were inhibited by ω-phthalimidoalkyl aryl ureas to a lesser extent.
- Dato, Florian M.,Sheikh, Miriam,Uhl, Rocky Z.,Schüller, Alexandra W.,Steinkrüger, Michaela,Koch, Peter,Neud?rfl, J?rg-Martin,Gütschow, Michael,Goldfuss, Bernd,Pietsch, Markus
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supporting information
p. 1833 - 1847
(2018/09/10)
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- DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS
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A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keap1-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.
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Paragraph 0439
(2018/06/09)
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- Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis
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Bisphosphonates such as zoledronic, alendronic and risedronic acids are a class of drugs clinically used to prevent bone density loss and osteoporosis. Novel P-C-P bisphosphonates were synthesized for targeting human farnesyl pyrophosphate synthase (hFPPS) and human geranylgeranyl pyrophosphate synthase (hGGPPS), key enzymes of the mevalonate pathway, and capable of anti-proliferative action on a number of cell lines (PC3, MG63, MC3T3, RAW 264.7, J774A.1, bone marrow cells and their co-colture with PC3) involved in bone homeostasis, bone formation and death. Among sixteen compounds, [1-hydroxy-2-(pyrimidin-2-ylamino)ethane-1,1-diyl]bis(phosphonic acid) (10) was effective in reducing PC3 and RAW 264.7 cell number in crystal-violet and cell-dehydrogenase activity assays at 100 μM concentration. 10 reduced differentiated osteoclasts number similarly with zoledronic acid in osteoclastogenesis assay. At nanomolar concentrations, 10 was more effective than zoledronic acid in inducing mineralization in MC3T3 and murine bone marrow cells. Further, 10 significantly inhibited the activity of hFPPS showing an IC50 of 0.31 μM and a remarkable hydroxyapatite binding of 90%. Docking calculations were performed identifying putative interactions between some representative novel bisphosphonates and both hFPPS and hGGPPS. Then, 10 was found to behave similarly or even better than zoledronic acid as a anti-resorptive agent.
- Savino, Salvatore,Toscano, Annamaria,Purgatorio, Rosa,Profilo, Emanuela,Laghezza, Antonio,Tortorella, Paolo,Angelelli, Mariacristina,Cellamarea, Saverio,Scala, Rosa,Tricarico, Domenico,Thomas Marobbio, Carlo Marya,Perna, Filippo,Vitale, Paola,Agamennone, Mariangela,Dimiccoli, Vincenzo,Tolomeo, Anna,Scilimati, Antonio
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p. 184 - 200
(2018/09/18)
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- Direct, visible light-sensitized benzylic C[sbnd]H fluorination of peptides using dibenzosuberenone: selectivity for phenylalanine-like residues
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A visible light-sensitized benzylic sp3C[sbnd]H fluorination protocol using dibenzosuberenone (5?mol?%) and Selectfluoris optimized for the direct functionalization of phenylalanine-like residues in short chain peptides. Amino acids, dipeptides, and tripeptides undergo benzylic fluorination with remarkable regioselectivity in the presence of protected basic, acidic, and nonpolar side chains (including those with tertiary sites). Additionally, protecting group compatibility, a gram scale application, and competition experiments were explored.
- Bume, Desta Doro,Pitts, Cody Ross,Jokhai, Rayyan Trebonias,Lectka, Thomas
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supporting information
p. 6031 - 6036
(2016/09/16)
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- HETEROARYL PYRIDONE AND AZA-PYRIDONE AMIDE COMPOUNDS
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Heteroaryl pyridone and aza-pyridone amide compounds of Formula (I) are provided, and various substituents including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk, and for treating cancer and immune disorders such as inflammation mediated by Btk. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 103
(2015/01/16)
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- A facile approach to β-amino acid derivatives via palladium-catalyzed hydrocarboxylation of enimides with formic acid
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An effective Pd(0)-catalyzed hydrocarboxylation of enimides with formic acid in the presence of a catalytic amount of HCOOPh is described. A variety of β-amino acid derivatives are obtained in good yields with high regioselectivities without using external toxic CO gas.
- Dai, Jie,Ren, Wenlong,Wang, Haining,Shi, Yian
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supporting information
p. 8429 - 8432
(2015/08/06)
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- Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes
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A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a "one pot" condensation reaction to α-amino acids. All phthaloyl amino acid derivatives presented anti-oral inflammatory activity, but compounds 2e and 2g were found to possess the best activities comparable to thalidomide.Most of the compounds effectively suppressed nitric oxide production inmurine cells stimulatedwith lipopolysaccharide. N-phthaloyl amino acids did not exhibit any significant cytotoxicity in vitro when tested against tumor cells as well as a spleen cell culture of BALB/c mice. Compounds 2a, 2g, and 2h were able to inhibit TNF-α and IL-1β production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity. Springer Science+Business Media 2013.
- Leite, Ana Cristina Lima,Barbosa, Fabio Fernandes,Cardoso, Marcos Verissimo De Oliveira,Moreira, Diogo R. M.,Coelho, Lucas Cunha D.,Da Silva, Elany Barbosa,Filho, Gevanio Bezerra De Oliveira,De Souza, Valdenia Maria Oliveira,Pereira, Valeria Rego A.,Reis, Luiza De C.,Ferreira, Paulo Michel Pinheiro,Pessoa, Claudia,Wanderley, Almir Goncalves,Mota, Fernanda Virginia B.,Da Silva, Teresinha G.
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p. 1701 - 1708
(2014/05/06)
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- TETRAHYDROISOQUINOLIN-2-YL-(QUINAZOLIN-4-YL) METHANONE COMPOUNDS AS CANCER CELL GROWTH INHIBITORS
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Tetrahydroisoquinolin-2-yl-(quinazolin-4-yl)methanone derivatives represented by formula (I), pharmacologically acceptable salts thereof, and compositions containing such compounds are described. Methods for treating hyperproliferative disorders by administering the compounds are also described. 1,2,3,4-tetrahydroisoquinoline derivatives for making tetrahydroisoquinolin-2-yl-(quinazolin-4-yl)methanone compounds are also described.
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Page/Page column 35
(2014/09/29)
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- Synthesis and in vitro and in vivo characterization of highly β1-selective β-adrenoceptor partial agonists
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β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-selective molecules exist. To address this clinical need, we re-evaluated LK 204-545 (1),(1) a selective β1-adrenoceptor antagonist, and discovered it possessed significant partial agonism. Removal of 1's aromatic nitrile afforded 19, a ligand with similar β1-adrenoceptor selectivity and partial agonism (log KD of -7.75 and -5.15 as an antagonist of functional β1- and β2-mediated responses, respectively, and 34% of the maximal response of isoprenaline (β1)). In vitro β-adrenoceptor selectivity and partial agonism of 19 were mirrored in vivo. We designed analogues of 19 to improve affinity, selectivity, and partial agonism. Although partial agonism could not be fully attenuated, SAR suggests that an extended alkoxyalkoxy side chain, alongside substituents at the meta- or para-positions of the phenylurea, increases ligand affinity and β1-selectivity.
- Mistry, Shailesh N.,Baker, Jillian G.,Fischer, Peter M.,Hill, Stephen J.,Gardiner, Sheila M.,Kellam, Barrie
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supporting information
p. 3852 - 3865
(2013/07/05)
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- Direct amide formation from N-arylglycine ethyl esters and carboxylic acids catalysed by phenylboronic acid
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The phenylboronic acid-catalysed reaction of an N-arylglycine ethyl ester with various carboxylic acids, including N-acyl-N-phenylglycines, directly affords an amide or a dipeptide in 13-73% yields.
- Huang, Wenhua,Sha, Wen-Bin
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p. 460 - 463
(2013/09/12)
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- A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter
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A novel fluorescent ligand was synthesized as a high-affinity, high specificity probe for visualizing the serotonin transporter (SERT). The rhodamine fluorophore was extended from an aniline substitution on the 5-position of the dihydroisobenzofuran ring of citalopram (2, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5- carbonitrile), using an ethylamino linker. The resulting rhodamine-labeled ligand 8 inhibited [3H]5-HT uptake in COS-7 cells (Ki = 225 nM) with similar potency to the tropane-based JHC 1-064 (1), but with higher specificity towards the SERT relative to the transporters for dopamine and norepinephrine. Visualization of the SERT with compound 8 was demonstrated by confocal microscopy in HEK293 cells stably expressing EGFP-SERT.
- Zhang, Peng,Jorgensen, Trine Nygaard,Loland, Claus J.,Newman, Amy Hauck
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supporting information
p. 323 - 326
(2013/02/23)
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- DIRECT INHIBITORS OF KEAP1-NRF2 INTERACTION AS ANTIOXIDANT INFLAMMATION MODULATORS
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A method of identifying compounds as direct inhibitors of Keap1-Nrf2 interaction through high-throughput screening and lead development. The direct inhibitors of Keap1-Nrf2 interaction are more specific and free of various undesirable effects than existing indirect inhibitors, and are potential drug candidates of chemopreventive and therapeutic agents for treatment of various diseases or conditions involving oxidative stress and/or inflammation, including but not limited to cancers, diabetes, Alzheimer's, and Parkinson's. Novel compounds are identified and methods of preventing or treating diseases or conditions related to Keapl-Nrf2 interaction activity by use of the novel compounds identified or compositions containing such compounds are also disclosed.
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Page/Page column 85
(2013/05/22)
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- Development of a practical and scalable synthesis of (R)- and (S)-3-amino-2-[(benzyloxy)methyl]propan-1-ol monohydrochloride: A useful C-4 Chiral Building Block
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The development of a practical and scalable synthesis of a C-4 chiral amine building block (R)-1·HCl and (S)-1·HCl is described. This important chiral intermediate (R)-1·HCl is efficiently synthesized from the commercially available, inexpensive, and simple 2-(hydroxymethyl)-1,3- propanediol (31) using lipase-catalyzed enantioselective hydrolysis as a key reaction. Development resulted in a telescoped process that was operated successfully and reproducibly in a pilot-plant-scale synthesis, and 22 kg of chiral amine (R)-1·HCl was prepared in the first scale-up synthesis. This synthetic method is also useful for preparation of the important chiral building block (S)-1·HCl, which is the enantiomer of (R)-1·HCl.
- Yoshida, Shinya,Obitsu, Kazuyoshi,Hayashi, Yasumasa,Shibazaki, Mitsuyoshi,Kimura, Takenori,Takahashi, Takumi,Asano, Toru,Kubota, Hirokazu,Mukuta, Takashi
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p. 1527 - 1537
(2013/02/23)
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- PHENOXYPROPANOL DERIVATIVES AND THEIR USE IN TREATING CARDIAC AND CARDIOVASCULAR DISEASES
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A compound of formula I-0, and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: wherein Z1 is C1-C4 linear or branched alkyl or alkenyl; R4 is selected from unsubstituted and substituted C3-C8 cycloalkyl, C1-C8 linear or branched alkyl, C2-5 alkenyl, C6-C10 heteroaryl or aryl, or C3-C8 heterocyclyl which may be part unsaturated, and combinations thereof; is linear C2-3 alkylene,; X1 is selected from NH and O; X2 is selected from unsaturated C and unsaturated S; and X3 is selected from NH and CH2; or one of X1 and X3 is a single bond; or X1 is O and X2 and X3 together are a single bond; and R7 is selected from oxo, F, Cl, Br, CN, NH2, NR92, NO2, CF3, OR9, COR9, OCOR9, COOR9, NR9COR9, CONR92 SO2NR92, NR9SO2R9; and R8 is selected from C1-5 alkyl, C1-5 alkoxyl, C2-5 alkenyl or alkynyl, C6-10) aryl and C3-8 cycloalkyl and combinations thereof, which may be unsubstituted or f urther substituted by one or more F, Cl, Br, CN, NH2, NR32, NO2, CF3; and R9 is selected from H and a group R8 as hereinbefore defined; n7 and n8 and the sum thereof are independently selected from zero and the whole number integer 1 to 4; processes for the preparation thereof, compositions and uses.
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Page/Page column 34
(2012/02/01)
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- Defining the mechanism of action and enzymatic selectivity of psammaplin A against its epigenetic targets
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Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the molecular features of this molecule responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC50 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotoxicity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor.
- Baud, Matthias G. J.,Leiser, Thomas,Haus, Patricia,Samlal, Sharon,Wong, Ai Ching,Wood, Robert J.,Petrucci, Vanessa,Gunaratnam, Mekala,Hughes, Siobhan M.,Buluwela, Lakjaya,Turlais, Fabrice,Neidle, Stephen,Meyer-Almes, Franz-Josef,White, Andrew J. P.,Fuchter, Matthew J.
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scheme or table
p. 1731 - 1750
(2012/04/23)
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- Preparation of the β2-homoselenocysteine derivatives Fmoc-(S)-β2hSec(PMB)-OH and Boc-(S)-β2hSec(PMB)- OH for solution and solid-phase peptide synthesis
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Fmoc-β2hSer(tBu)-OH was converted to Fmoc-β2hSec(PMB)-OH in five steps. To avoid elimination of HSeR, the selenyl group was introduced in the second last step (Fmoc- β2hSer(Ts)-OAll→Fmoc-β2hSec(PMB)-OAll). In a similar way, the N-Boc-protected compound was prepared. With the β2hSe-derivatives, 21 β2-amino-acid building blocks with proteinogenic side chains are now available for peptide synthesis. Copyright
- Patora-Komisarska, Krystyna,Jadwiga Podwysocka, Dominika,Seebach, Dieter
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scheme or table
p. 1 - 17
(2011/03/17)
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- Synthesis and antiviral activity of novel 1,3,4-thiadiazine derivatives
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A series of novel 1,3,4-thiadiazine derivatives were synthesized via chemical optimization on phthiobuzone. Their anti-herpes simplex virus (HSV) activities in vitro were also tested. Several compounds exhibited more highly potent anti-HSV activity and much higher selectivity index (SI) values than those of phthiobuzone. The most potent anti-HSV compound was 4f, which showed marked inhibition against HSV-1 (IC50=77.04μg/ml) and HSV-2 (IC50=30.00μg/ml). Meanwhile it had low cytotoxicity (CC 50=1000.00μg/ml), resulting in high (SIHSV-1= 12.98, SIHSV-2=33.33, respectively). Furthermore, a computational study for prediction of absorption, distribution, metabolism, excretion (ADME) properties of compound 4f was performed by determination of topological polar surface area, absorption and Lipinski parameters.
- Yang, Yajun,Feng, Ziming,Jiang, Jianshuang,Yang, Yanan,Pan, Xiandao,Zhang, Peicheng
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scheme or table
p. 1016 - 1019
(2011/10/08)
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- Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogues
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The first total synthesis of the indole alkaloids (±)-aplicyanins A, B, and E, plus 17 analogues, all in racemic form, is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the nature of the substituents on the indole nitrogen (H, Me, or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and 14 of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the presence of the bromine at position 5 of the indole is critical to activity, as well as the acetyl group on the imine nitrogen does in some compounds. 2009 American Chemical Society.
- ?í?a, Miroslav,Pla, Daniel,Altuna, Marta,Francesch, Andrés,Cuevas, Carmen,Albericio, Fernando,álvarez, Mercedes
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body text
p. 6217 - 6223
(2010/03/24)
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- The selective quantification of iron by hexadentate fluorescent probes
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The synthesis of four hexadentate fluorescent probes is described, where the fluorescent moiety is based on either coumarin or fluorescein and the chelating moiety is based on either 3-hydroxypyridin-4-one or 3-hydroxypyran-4-one. The fluorescence is quenched when the probe chelating moieties bind iron. The probes were found to be selective for iron over other metals such as Cu, Zn, Ni, Mn and Co. The effect of Cu on fluorescence quenching can be eliminated in the presence of N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine. Competition studies demonstrate that the exchange of iron between pyridinone-based probes and apotransferrin is very slow. The ability to scavenge iron from oligomeric iron(III) citrate complexes demonstrate that the pyridinone probes scavenges iron faster than deferiprone and desferrioxamine. The fluorescence intensity of the fluorescein-based probe is quantitatively related to the iron concentration with the limit of detection being 10-8 M.
- Ma, Yong Min,Hider, Robert C.
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experimental part
p. 8093 - 8101
(2010/03/30)
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- Synthesis of phosphonodipeptide conjugates of ursolic acid and their homologs
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To prepare novel derivatives of naturally bioactive 3β-hydroxy-urs-12- en-28-oic acid (ursolic acid) with unusual properties and broad spectrum of activities, a number of chemical reactions were conducted. First, a variety of a-aminophosphonates were prepared by a series of reactions involving the three-component Mannich type reaction as a key step. Second, an array of phosphonodipeptides and their homologs was synthesized through multistep reactions including condensation of phthalic anhydride with glycine or β-alanine, chlorination of N-blocked amino acids, coupling of acid chloride with α-aminophosphonates and sequential hydrazinolysis. Finally, new classes of phosphonodipeptide conjugates of ursolic acid and their homologs were obtained by condensation of 3β-acetoxy-urs-12-en-28-oyl chloride with phosphonodipeptides and their homologs.
- Deng, Sheng-Lou,Baglin, Isabelle,Nour, Mohammed,Cave, Christian
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- Syntheses of phosphonic esters of alendronate, pamidronate and neridronate
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Several synthetic pathways for obtaining phosphonic esters of the amino bisphosphonic acids (NBPs) pamidronate, alendronate and neridronate were investigated. The general guideline was to react N-protected amino acids activated as phthalimide esters or as acyl chlorides. Succinimide esters were found less reactive and quickly abandoned. γ-Lactam formation arises when starting from Boc- or Cbz-protected amino acids. The phthalimide N-protecting group allowed access to alkyl or aryl mono-, di- (symmetric or not) and triesters of these three NBPs in high yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Guenin, Erwann,Monteil, Maelle,Bouchemal, Nadia,Prange, Thierry,Lecouvey, Marc
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p. 3380 - 3391
(2008/02/10)
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- Iron binding dendrimers: A novel approach for the treatment of haemochromatosis
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A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.
- Zhou, Tao,Neubert, Hendrik,Liu, Ding Yong,Liu, Zu Dong,Ma, Yong Min,Kong, Xiao Le,Luo, Wei,Mark, Sykes,Hider, Robert C.
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p. 4171 - 4182
(2007/10/03)
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- In situ generation of o-lodoxybenzoic acid (IBX) and the catalytic use of it in oxidation reactions in the presence of oxone as a co-oxidant
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(Chemical Equation Presented) Catalytic use of o-iodoxybenzoic acid (IBX) in the presence of Oxone as a co-oxidant is demonstrated for the oxidation of primary and secondary alcohols in user- and eco-friendly solvent mixtures. Also demonstrated is the in situ (re)oxidation of 2-iodosobenzoic acid (IBA) and even commercially available 2-iodobenzoic acid (2IBAcid) by Oxone to IBX allowing one to use these less hazardous reagents, in place of potentially explosive IBX, as catalytic oxidants.
- Thottumkara, Arun P.,Bowsher, Michael S.,Vinod, Thottumkara K.
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p. 2933 - 2936
(2007/10/03)
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- Nitrogen-based camptothecin derivatives
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(20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an aminoalkanoic acid or an imidoalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.
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- Preparation of protected β2- and β3- homocysteine, β2- and β3-homohistidine, and β2-homoserine for solid-phase syntheses
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The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β-peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β3-homoamino acid derivatives were obtained by Arndt-Eistert methodology from Boc-His(Ts)-OH and Fmoc-Cys(PMB)-OH (Schemes 2-4), with the side-chain functional groups' reactivities requiring special precautions. The β2-homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti-enolates to formaldehyde (generated in situ from trioxane) and subsequent functional-group manipulations. These include OH → OtBu etherification (for β2hSer; Schemes 5 and 6), OH → STrt replacement (for β2hCys; Scheme 7), and CH 2OH → CH2N3 → CH2NH 2 transformations (for β2hHis; Schemes 9-11). Including protection/deprotection/re-protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (tR), melting points, optical rotations, HPLC on chiral columns, IR, 1H- and 13C-NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X-ray crystal-structure analysis.
- Lelais, Gerald,Micuch, Peter,Josien-Lefebvre, Delphine,Rossi, Francesco,Seebach, Dieter
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p. 3131 - 3159
(2007/10/03)
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- Structure-based de novo design of ligands using a three-dimensional model of the insulin receptor
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For the first time, a three-dimensional model of the insulin receptor is used in the de novo design of novel ligands that potentially mimic interactions of insulin at its receptor. Compound 4 competed with insulin as seen in autophosphorylation assays and inhibited up to 68% of IR autophosphorylation at 300 μM of 4 in 3T3IR cells induced by 1 nM insulin. This model provides a basis for the design of potent insulin receptor ligands.
- Tan, Christopher,Wei, Lianhu,Ottensmeyer, F. Peter,Goldfine, Ira,Maddux, Betty A.,Yip, Cecil C.,Batey, Robert A.,Kotra, Lakshmi P.
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p. 1407 - 1410
(2007/10/03)
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- Nitrogen-based camptothecin derivatives
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(20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an aminoalkanoic acid or an imidoalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.
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- Nitrogen-based camptothecin derivatives
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(20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an aminoalkanoic acid or an imidoalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.
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- Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids
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In order to study the influence of the length of the amino acid chain of N,N-phthaloyl-amino acid amides as analogues of the former anticonvulsant taltrimide on the seizure-antagonizing activity glycine, β-alanine and γ-aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine-derived amides showed a higher activity than the β-alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine derivatives. The N,N-phthaloyl-glycine amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylene-tetrazole. The ED50 of N,N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal administration to mice was 19.1 mg/kg. On a molar basis this activity is comparable to the activity of phenytoin with little toxicity in the rotorod test. In conclusion, N,N-phthaloyl-glycine amides might represent promising antiepileptic drugs.
- Usifoh, Cyril O.,Lambert, Didier M.,Wouters, Johan,Scriba, Gerhard K.E.
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p. 323 - 331
(2007/10/03)
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- Self-assembling heteropolymetallic chelates as imaging agents and radiopharmaceuticals
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Metal complexes of new ligands of the formula STR1 are useful as agents for medical imaging, particularly MRI, for in vitro or in vivo diagnostic or as radiopharmaceuticals. In these compounds, X--R1 --Y is a coordinating group able to form a highly stable complex with metal ions. Suitable units are for example derivatives of ortho-phenanthroline or of an hydroxamic acid. R2 and R3 are reactive functions such as amines or carboxylic groups. R4 and R5 are ligands, for instance diethylenetriaminepentaacetic acid 1,4,7,10-tetraacetic acid (DTPA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,8,11-tetraazacyclotetradecane-N, N', N", N'"-tetraacetic acid (TETA), of a different type than the X--R1 --Y units and able to strongly encapsulate metal ions with which the X--R1 --Y moieties form less stable chelates. Stable high molecular weight multimetallic entities are spontaneously formed by these ligands that spontaneously associate around metal ions through the X--R1 --Y units. Higher relaxivities thus are achieved. Mixed-complexes containing two different radionuclides are also obtained thus allowing imaging and therapy with one single chelate.
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- Exploratory studies probing the intermediacy of azomethine ylides in the photochemistry of N-phthaloyl derivatives of α-amino acids and β-amino alcohols
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Exploratory photochemical studies with N-phthaloyl derivatives of glutamic acid, aspartic acid, serine, threonine and analogous carboxylic acids and alcohols have been conducted to determine the generality of azomethine ylide forming decarboxylation and retro-aldol fragmentation reactions. Preferences in the competition between these excited state reaction pathways have been determined by studies with phthalimides which contain both α-amino acid and β-aminoethanol groups.
- Yoon, Ung Chan,Lee, Chan Woo,Oh, Sun Wha,Mariano, Patrick S.
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p. 11997 - 12008
(2007/10/03)
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- Development of monoclonal ELISAs for azinphos-methyl. 1. Hapten synthesis and antibody production
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The development of monoclonal antibody-based enzyme-linked immunosorbent assays for azinphosmethyl is described. A panel of haptens was synthesized for immunoconjugate preparation, and a series of haptens for heterologous, coating or tracer, conjugates was also prepared. Hapten synthesis was based on a strategy in which only a fragment of the whole target molecule was present (fragmentary haptens). From immunized mice, a set of monoclonal antibodies was obtained and ELISA sensitivities were assayed in different formats. Affinities estimated as I50 values in the low nanomolar range for azinphos-methyl and phosmet were observed for several monoclonal antibodies in the conjugate-coated format and in the antibody-coated format under nonoptimized assay conditions.
- Mercader, Josep V.,Montoya, Angel
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p. 1276 - 1284
(2007/10/03)
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- 6-N-(N-methylanthranylamido)-4-oxo-hexanoic acid : A new fluorescent protecting group applicable to a new DNA sequencing method
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6-Amino-4-oxo-hexanoic acid with a fluorescent probe attached to the amino function, derivative of the levulinic acid has been developed for protection of hydroxyl groups. It is introduced by reaction of its symetrical anhydride and rapidly removed under mild conditions using a hydrazine- pyridinium acetate buffer at near neutral pH and room temperature. It can be used within the scope of a new DNA sequencing method and as a sensitive detectable protecting group.
- Rasolonjatovo, Isabelle,Sarfati, Simon R.
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p. 2021 - 2025
(2007/10/03)
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- Process for preparing acetoxyazetidinone derivative and intermediate thereof
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An N-?2-(1-hydroxyethyl)-3-oxopropyl!amine compound of the formula ?III!: STR1 wherein Ring B represents a benzene ring which may be substituted; W represents oxygen atom or sulfur atom; Y represents oxygen atom, sulfur atom or N R0, R0 represents hydrogen atom or a substituent; Z represents a substituted methylene group which contains at least one chiral center; R5 represents an aralkyloxycarbonyl group or an alkoxycarbonyl group; R6 represents hydrogen atom, an aralkyl group, an acyloxy group, a tri-substituted silyloxy group or an alkoxy group; or both of R5 and R6 bond at their termini and combine with the adjacent nitrogen atom to form phthalimido group, and a process thereof are disclosed. Said compound ?III! is useful as a starting compound of β-lactam antibacterial agents.
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- Synthesis and neuropeptide Y Y1 receptor antagonistic activity of N,N-disubstituted ω-guanidino- and ω-aminoalkanoic acid amides
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Patent arpromidine-type histamine H2 receptor agonists such as BU-E-76 (He 90481) were among the first non-peptides reported to display weak neuropeptide Y (NPY) Y1 receptor antagonist activity. In search of new chemical leads for the development of more potent NPY antagonists, a series of N,N-disubstituted ω-guanidino and ω-aminoalkanoic acid amides were synthesized on the basis of structure-activity relationships and molecular modeling studies of arpromidine and related imidazolylpropylguanidines. In one group of compounds the imidazole ring was retained whereas in the second group it was replaced with a phenol group representing a putative mimic of Tyr36 in NPY. Although the substitution patterns have not yet been optimized, the title compounds are NPY Y1 antagonists in human erythroleukemia (HEL) cells (Ca2+ assay) achieving pK(B) values in the range of 6.3-6.6. For representative new substances tested in the isolated guinea pig right atrium histamine H2 receptor agonism could not be found. In the N-(diphenylalkyl)amide series, compounds with a trimethylene chain were more active Y1 antagonists than the ethylene homologs. Concerning the spacer in the ω-amino or ω-guanidinoalkanoyl portion, the best activity was found in compounds with a four- or five-membered alkyl chain or a 1,4-cyclohexylene group. Surprisingly, in contrast to the phenol series, in the imidazole series the compounds with a side chain amino group turned out to be considerably mere potent than the corresponding strongly basic guanidines. Thus, the structure-activity relationships appear to be different for the diphenylalkylamide NPY antagonists with one or two basic groups.
- Mueller, Manfred,Knieps, Sebastian,Gessele, Karin,Dove, Stefan,Bernhardt, Guenther,Buschauer, Armin
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p. 333 - 342
(2007/10/03)
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- Synthesis of Medium- and Large-Ring Compounds Initiated by Photochemical Decarboxylation of ω-Phthalimidoalkanoates
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The synthesis of a variety of hydroxylactams from ω-phthalimidoalkanoates using a triplet-sensitized photodecarboxylation reaction initiated by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine-1,5-dione 7) to 26 (cyclodipeptide 26e). Ground-state template formation is proposed as the explanation for the high efficiency of this reaction and for the decrease in reactivity in the presence of organic bases instead of metal carbonates. The crucial step in this macrocyclization reaction seems to be the protonation of the intermediary ketyl radiais (Scheme 4). Spacer groups investigated were alkyl chains (C3-C11: 5c-h, 11a, 12), ether (16, 18), ester (20, 22), and amide (26a-f) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intra-vs. intermolecular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cf. products 11 and 12) in contrast to comparable singlet reactions. Except for the lactones 22, all products were stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23, probably via an intermediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in 27a and 27b), probably the consequence of a strong intramolecular H-bond (Scheme 10).
- Griesbeck, Axel G.,Henz, Andreas,Kramer, Wolfgang,Lex, Johann,Nerowski, Frank,Oelgemoeller, Michael,Peters, Karl,Peters, Eva-Maria
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p. 912 - 933
(2007/10/03)
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