- L-DOPA Dioxygenase Activity on 6-Substituted Dopamine Analogues
-
Dioxygenase enzymes are essential protein catalysts for the breakdown of catecholic rings, structural components of plant woody tissue. This powerful chemistry is used in nature to make antibiotics and other bioactive materials or degrade plant material, but we have a limited understanding of the breadth and depth of substrate space for these potent catalysts. Here we report steady-state and pre-steady-state kinetic analysis of dopamine derivatives substituted at the 6-position as substrates of L-DOPA dioxygenase, and an analysis of that activity as a function of the electron-withdrawing nature of the substituent. Steady-state and pre-steady-state kinetic data demonstrate the dopamines are impaired in binding and catalysis with respect to the cosubstrate molecular oxygen, which likely afforded spectroscopic observation of an early reaction intermediate, the semiquinone of dopamine. The reaction pathway of dopamine in the pre-steady state is consistent with a nonproductive mode of binding of oxygen at the active site. Despite these limitations, L-DOPA dioxygenase is capable of binding all of the dopamine derivatives and catalyzing multiple turnovers of ring cleavage for dopamine, 6-bromodopamine, 6-carboxydopamine, and 6-cyanodopamine. 6-Nitrodopamine was a single-turnover substrate. The variety of substrates accepted by the enzyme is consistent with an interplay of factors, including the capacity of the active site to bind large, negatively charged groups at the 6-position and the overall oxidizability of each catecholamine, and is indicative of the utility of extradiol cleavage in semisynthetic and bioremediation applications.
- Goldberg, Alexander M.,Robinson, Miranda K.,Starr, Erykah S.,Marasco, Ryan N.,Alana, Alexa C.,Cochrane, C. Skyler,Klugh, Kameron L.,Strzeminski, David J.,Du, Muxue,Colabroy, Keri L.,Peterson, Larryn W.
-
p. 2492 - 2507
(2021/08/18)
-
- Catechol reactivity: Synthesis of dopamine derivatives substituted at the 6-position
-
Dopamine is a ubiquitous neurotransmitter essential in the proper functioning of the human body. In addition to this critical role, the catecholamine core has shown utility as a scaffold for numerous drugs and in other applications, like metal detection and adhesive materials. Substituents at the 6-position of dopamine’s catechol core can modulate its stereoelectronic properties, the acidity of its phenolic hydroxyl groups, and the overall hydrophobicity of the molecule. Herein, we report the synthesis of a series of four novel dopamine analogues substituted at the 6-position of catechol core. The1H NMR chemical shift of the aromatic proton meta to the substituent correlated strongly with the Hammett σmconstant, confirming the electronic properties of substituents.
- Rote, Jennifer C.,Malkowski, Sarah N.,Cochrane, C. Skyler,Bailey, Gabrielle E.,Brown, Noah S.,Cafiero, Mauricio,Peterson, Larryn W.
-
supporting information
p. 435 - 441
(2017/02/24)
-
- CuI-catalyzed coupling of gem-dibromovinylanilides and sulfonamides: An efficient method for the synthesis of 2-amidoindoles and indolo[1,2-a] quinazolines
-
A Cu(I)-catalyzed, intermolecular protocol for the synthesis of 2-amidoindoles and tetrahydroindolo[1,2-a]quinazolines in shorter time and high yields is reported. The key highlight of this disclosure is the formation of 2-amidoindole and tetrahydroindolo[1,2-a]quinazoline moieties directly from gem-dibromovinylanilides and sulfonamides in a one-pot fashion through the in situ formation of ynamides followed by a base-promoted intramolecular hydroamidation.
- Kiruthika, Selvarangam E.,Perumal, Paramasivan Thirumalai
-
supporting information
p. 484 - 487
(2014/04/03)
-
- FSH RECEPTOR ANTAGONISTS
-
The invention relates to FSH receptor antagonist according to general formula (I) or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders
- -
-
-
- Phosphane-free Pd0-catalyzed cycloamination and carbonylation with Pd(OAc)2 and Cu(OAc)2 in the presence of K 2CO3: Preparation of benzocyclic amines and benzolactams
-
Phosphane-free Pd0-catalyzed intramolecular aromatic amination was studied. o-Halophenethylamines and 3-(o-halophenyl)propylamines were found to be transformed into indolines and quinolines in a catalytic system based on Pd(OAc)2 and Cu(OAc)2 in the presence of K 2CO3. Application of the method to substrates containing isoquinoline rings- the 1-(o-bromobenzyl)-3,4-dihydroisoquinolines 6, the 1-(o-bromobenzyl)-1,2,3,4-tetrahydroisoquinolines 7, and the 1-(o-bromophenethyl)isoquinolines 9- provided the indolo[2,1-a]isoquinoline and dibenzo[a,f]quinolizine ring systems 8 and 10. Extension of the method to β-carbolines (compounds 11, 12, and 17) produced the benz[f]indolo[2,3-a] indolizine-13-ones 15 and the benz[f]indolo[2,3-a]quinolizine 18. The benzo[f]pyrido[3,4-a]indolizine and indolo[f]pyrido[3,4-a]indolizin-12-one ring systems 27 and 31 were built in a similar manner. It was also found that under an atmosphere of CO the same catalytic system produced the corresponding benzolactams, the isoquino[2,1-a][2,7]naphthyridine 34 and the indolo[2,3-a]pyrido[g]quinolizin-8-one 36 [(±)-dihydronauclefine] in good yields. Copyright
- Harada, Rika,Nishida, Naoto,Uchiito, Shiho,Onozaki, Yu,Kurono, Nobuhito,Senboku, Hisanori,Masao, Tokuda,Ohkuma, Takeshi,Orito, Kazuhiko
-
experimental part
p. 366 - 379
(2012/02/04)
-
- Improved arene fluorination methodology for I(III) salts
-
(Equation Presented). The use of low polarity aromatic solvents (benzene or toluene) and/or the removal of inorganic salts results in dramatically improved yields of fluorinated arenes from diaryliodonium salts. This methodology is shown to "scale down" to the conditions used typically for radiotracer synthesis.
- Wang, Bijia,Qin, Linlin,Neumann, Kiel D.,Uppaluri, Shriharsha,Cerny, Ronald L.,DiMagno, Stephen G.
-
supporting information; experimental part
p. 3352 - 3355
(2010/11/02)
-
- FLUORINATION OF AROMATIC RING SYSTEMS
-
This disclosure relates to reagents and methods useful in the synthesis of aryl fluorides, for example, in the preparation of 18F labeled radiotracers. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.
- -
-
Page/Page column 41
(2010/05/13)
-
- Regioselective, photochemical bromination of aromatic compounds using N-bromosuccinimide
-
Regioselective nuclear bromination of aromatic compounds is investigated with N-bromosuccinimide as the brominating agent under UV irradiation to afford the corresponding brominated compounds. The reaction proceeds at ambient temperature (30 ± 2 °C) without any catalyst. In most of the reactions, regioselectively mono-brominated products are obtained in good to high yields. The conversion and selectivity for bromination depend on the nature of the substituent on the aromatic ring.
- Chhattise, Prakash K.,Ramaswamy,Waghmode, Suresh B.
-
p. 189 - 194
(2008/03/30)
-
- Generation of a small library of highly electron-rich 2-(hetero)aryl- substituted phenethylamines by the Suzuki-Miyaura reaction: A short synthesis of an apogalanthamine analogue
-
The Suzuki-Miyaura reaction is presented as a versatile procedure for the synthesis of a small library of highly electronrich 2-[4,5-dimethoxy-2-(hetero) arylphenyl]ethylamines. Microwave-irradiation accelerates the reaction tremendously and furnishes superior yields. The difficult oxidative addition of the catalyst to a highly electron-rich and ortho-substituted system could be performed easily, and the proto-deboronation during cross-coupling reactions involving the highly electron-withdrawing (2-formylphenyl)boronic acid could be minimized. Enhanced yields and complete compatibility with aqueous conditions were found. This strategy was developed en route towards the synthesis of an apogalanthamine analogue. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Appukkuttan, Prasad,Orts, Amparo Baiget,Chandran, R. Prakash,Goeman, Jan. L.,Van Der Eycken, Johan,Dehaen, Wim,Van Der Eycken, Erik
-
p. 3277 - 3285
(2007/10/03)
-
- Photochemically induced cyclization of N-[2-(o-styryl)phenylethyl]acetamides and 5-styryl-1-methyl-1,2,3,4-tetrahydroisoquinolines: New total syntheses of 1-methyl-1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolines
-
Two new total syntheses of 1-methyl-1,2,3,4-dihydronaphtho[1,2-f]isoquinolines are based on photochemically induced cyclization of N-{2-[(E)-2-phenyl-1-etheynyl]phenylethyl]}acetamides or 1-methyl-5-[(E)-2-phenyl-1-ethenyl]-1,2,3,4-tetrahydroisoquinolines.
- Martínez, Elena,Estévez, Juan C,Estévez, Ramón J,Castedo, Luis
-
p. 1981 - 1986
(2007/10/03)
-
- Regioselective synthesis of isoquino[1,2-b][3]benzazepines (homoprotoberberines) through 11-membered-ring stilbene lactams obtained by radical macrocyclization
-
Silylated 11-membered-ring stilbene lactams 3 (E and Z) were easily prepared by intramolecular addition of an aryl radical to a trimethylsilylacetylene. Oxidation of their hindered stilbene double bonds with dioxiranes gave oxidative cleavage of their electron-rich aromatic rings. However, reduction of the amide to an amine functionality in both lactams (E and Z) triggers a regioselective [7,6]-transannular cyclization to isoquino[1,2-b][3]benzazepines (homoprotoberberines).
- Rodriguez, Gema,Castedo, Luis,Dominguez, Domingo,Saa, Carlos,Adam, Waldemar
-
p. 4830 - 4833
(2007/10/03)
-
- A Photochemical Synthesis of Benzindenoazepines
-
A novel synthesis of benzindenoazepine (10) has been achieved by photochemical cyclization of the bromo enaminone (8).On the other hand, irradiation of enolates and enamides failed to give the cyclized azepines.
- Fidalgo, Jesus,Castedo, Luis,Dominguez, Domingo
-
p. 581 - 590
(2007/10/02)
-
- An intramolecular aryne cycloaddition approach to phenanthrene alkaloids
-
A new synthesis of phenanthrene alkaloids which is based on the intramolecular Diels-Alder reaction between a styrene and an aryne is described.
- Estevez,Estevez,Castedo
-
p. 6883 - 6884
(2007/10/02)
-
- A Convenient Synthesis of Apogalanthamine Analogues as α-Adrenergic Blocking Agents using Zerovalent Nickel
-
The apogalanthamine analogues, 5,6,7,8-tetrahydrodibenzazocine (2) and its N-methyl and N-acetyl derivatives (1 and 3), and the methoxy derivatives (4, 5 and 9) of (1) were obtained in good yields by cyclization of the corresponding halogeno-N-benzyl-β-phenethylamines (10a, 11a-d, 12a,b and 13a-c) using stoichiometric amounts of zerovalent nickel generated in situ and potassium iodide.
- Kihara, Masaru,Itoh, Joji,Iguchi, Seiichiro,Imakura, Yasuhiro,Kobayashi, Shigeru
-
p. 157 - 177
(2007/10/02)
-