- Selectivity in sodium borohydride reduction of coumarin encapsulated in β-cyclodextrin
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The sodium borohydride reduction of coumarin to the corresponding alkanol and alkenol has been investigated in the presence and absence of β-cyclodextrin (β-CD). Excellent selectivity is observed when β-CD-coumarin complex is reduced in solid state at 0°C and the alkenol, cis-o-hydroxycinnamyl alcohol is the major product. Complex formation and the mode of substrate insertion into the CD cavity have been analysed using various physical methods.
- Pitchumani, Kasi,Velusamy, Ponnusamy,Srinivasan, Chockalingam
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Read Online
- A ring size-selective reduction of lactones using SmI2 and H2O
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The SmI2-H2O reducing system shows complete selectivity for six-membered lactones over other classes of lactone and esters. Experimental and computational studies suggest that the origin of the selectivity lies in the initial electro
- Duffy, Lorna A.,Matsubara, Hiroshi,Procter, David J.
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Read Online
- WDR5-MYC INHIBITORS
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Substituted N-phenyl sulfonamide compounds inhibit WDR5-MYC interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.
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Paragraph 00749-00750
(2021/02/05)
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- COMPOUNDS AND COMPOSITIONS FOR OCULAR DELIVERY
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The present invention provides new prodrags of Sunitinib, Brinzolamide, and Dorzolamide and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (TOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.
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Page/Page column 108; 217
(2020/05/12)
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- Probing the Existence of a Metastable Binding Site at the β2-Adrenergic Receptor with Homobivalent Bitopic Ligands
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Herein, we report the development of bitopic ligands aimed at targeting the orthosteric binding site (OBS) and a metastable binding site (MBS) within the same receptor unit. Previous molecular dynamics studies on ligand binding to the β2-adrenergic receptor (β2AR) suggested that ligands pause at transient, less-conserved MBSs. We envisioned that MBSs can be regarded as allosteric binding sites and targeted by homobivalent bitopic ligands linking two identical pharmacophores. Such ligands were designed based on docking of the antagonist (S)-alprenolol into the OBS and an MBS and synthesized. Pharmacological characterization revealed ligands with similar potency and affinity, slightly increased β2/β1AR-selectivity, and/or substantially slower β2AR off-rates compared to (S)-alprenolol. Truncated bitopic ligands suggested the major contribution of the metastable pharmacophore to be a hydrophobic interaction with the β2AR, while the linkers alone decreased the potency of the orthosteric fragment. Altogether, the study underlines the potential of targeting MBSs for improving the pharmacological profiles of ligands.
- Gaiser, Birgit I.,Danielsen, Mia,Marcher-R?rsted, Emil,R?pke J?rgensen, Kira,Wróbel, Tomasz M.,Frykman, Mikael,Johansson, Henrik,Br?uner-Osborne, Hans,Gloriam, David E.,Mathiesen, Jesper Mosolff,Sejer Pedersen, Daniel
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p. 7806 - 7839
(2019/09/07)
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- Design, Synthesis, and Cellular Uptake of Oligonucleotides Bearing Glutathione-Labile Protecting Groups
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Glutathione-labile protecting groups for phosphodiester moieties in oligonucleotides were designed, synthesized, and incorporated into oligonucleotides. The protecting groups on the phosphodiester moieties were cleaved in a buffer containing 10 mM glutath
- Saneyoshi, Hisao,Ohta, Takayuki,Hiyoshi, Yuki,Saneyoshi, Takeo,Ono, Akira
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supporting information
p. 862 - 866
(2019/02/14)
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- Towards practical earth abundant reduction catalysis: Design of improved catalysts for manganese catalysed hydrogenation
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Manganese catalysts derived from tridentate P,N,N ligands can be activated easily using weak bases for both ketone and ester hydrogenations. Kinetic studies indicate the ketone hydrogenations are 0th order in acetophenone, positive order in hydrogen and 1st order in the catalyst. This implies that the rate determining step of the reaction was the activation of hydrogen. New ligand systems with varying donor strength were studied and it was possible to make the hydrogen activation significantly more efficient; a catalyst displaying around a 3-fold increase in initial turn-over frequencies for the hydrogenation of acetophenone relative to the parent system was discovered as a result of these kinetic investigations. Ester hydrogenations and ketone transfer hydrogenation (isopropanol as reductant) are first order for both the substrate and catalysts. Kinetic studies also gained insight into catalyst stability and identified a working range in which the catalyst is stable throughout the catalytic reaction (and a larger working range where high yields can still be achieved). The new more active catalyst, combining an electron-rich phosphine with an electron-rich pyridine is capable of hydrogenating acetophenone using as little as 0.01 mol% catalyst at 65 °C. In all, protocols for reduction of 21 ketones and 15 esters are described.
- Widegren, Magnus B.,Clarke, Matthew L.
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p. 6047 - 6058
(2019/11/14)
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- Synthesis and PGE2 inhibitory activity of novel diarylheptanoids
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Prostaglandin E2 (PGE2) is a lipid mediator of inflammation and its inhibition has become a popular drug target due to its harmful physiological roles. Diarylheptanoids are one class of compounds that have shown successful inhibition of PGE2. This paper reports the synthesis and PGE2 inhibitory activity of a series of analogues of a naturally occurring diarylheptanoid. The most efficacious compounds were examined for dose-dependent PGE2 inhibition. Among several promising compounds, the lead candidate exhibited an IC50 value of 0.56 ng/μL or 1.7 μM with no detectable toxicity at the highest dose of 10 ng/μL.
- McLane, Richard D.,Le Cozannet-Laidin, Léon,Boyle, Maxwell S.,Lanzillotta, Lindsey,Taylor, Zachary L.,Anthony, Sarah R.,Tranter, Michael,Onorato, Amber J.
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supporting information
p. 334 - 338
(2018/02/15)
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- Ti-Catalyzed Synthesis of Exocyclic Allenes on Oxygen Heterocycles
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A general method for the straightforward synthesis of exocyclic allenes on five-, six-, seven-, and eight-membered oxygen heterocycles is described. A Barbier-type titanocene(III)-catalyzed cyclization of propargyl halides with a pendant carbonyl group is
- Padial, Natalia M.,Hernández-Cervantes, Carmen,Mu?oz-Bascón, Juan,Roldán-Molina, Esther,García-Martínez, Mireya,Ruiz-Muelle, Ana Belén,Rosales, Antonio,álvarez-Corral, Míriam,Mu?oz-Dorado, Manuel,Rodríguez-García, Ignacio,Oltra, J. Enrique
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p. 639 - 645
(2017/02/05)
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- Coordination Chemistry of an Unsymmetrical Naphthyridine-Based Tetradentate Ligand toward Various Transition-Metal Ions
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An unsymmetrical ligand, 2-(2-pyridinyl)-7-(pyrazol-1-yl)-1,8-naphthyridine (L5) was prepared for the construction of a series of dinuclear complexes. Treatment of L5with [Ru2(μ-OAc)4Cl] followed by anion metathesis afforded [(L5)(μ-OAc)3Ru2](PF6) (3). Reaction of L5with 2 equiv. of Ni(OAc)2provided [Ni4(L5)2(μ-OH)4(CF3COO)2](CF3COO)2(5). Reaction of [Re2(CO)8(CH3CN)2] with L5in a refluxing chlorobenzene solution gave a mixture of dirhenium (6) and monorhenium (7) complexes. The monocobalt complex 8 was obtained from complexation of L5with CoCl2. These new complexes were characterized by elemental analysis and spectroscopic techniques. The structures of complexes 3, 5 and 8 were further confirmed by X-ray crystallography. Nickel complex 5 was evaluated as a catalyst for reduction reactions involving the conversion of ester functionalities into their corresponding alcohols.
- Tsai, Bing-Chen,Liu, Yi-Hung,Peng, Shie-Ming,Liu, Shiuh-Tzung
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p. 2783 - 2790
(2016/07/11)
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- Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions
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NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.
- Nguyen, Thanh V. Q.,Yoo, Woo-Jin,Kobayashi, Shu
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supporting information
p. 452 - 458
(2016/02/12)
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- Evaluating a sodium dispersion reagent for the Bouveault-Blanc reduction of esters
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A new sodium dispersion reagent has been evaluated for the reduction of esters. Na-D15, a sodium dispersion with sodium particle size of 5-15 μm, is a nonpyrophoric reagent that can be handled in air. In this study, a broad range of aliphatic ester substrates were reduced to primary alcohols by Na-D15/i-PrOH with good yields. The method compares favorably with modern metal hydride reductions and is much safer and efficient than the traditional Bouveault-Blanc reduction.
- An, Jie,Work, D. Neil,Kenyon, Craig,Procter, David J.
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p. 6743 - 6747
(2014/08/05)
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- CYCLIC PEROXIDE OXIDATION OF AROMATIC COMPOUND PRODUCTION AND USE THEREOF
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The present invention provides a method for converting an aromatic hydrocarbon to a phenol by providing an aromatic hydrocarbon comprising one or more aromatic C-H bonds and one or more activated C-H bonds in a solvent; adding a phthaloyl peroxide to the solvent; converting the phthaloyl peroxide to a di-radical; contacting the di-radical with the one or more aromatic C-H bonds; oxidizing selectively one of the one or more aromatic C-H bonds in preference to the one or more activated C-H bonds; adding a hydroxyl group to the one of the one or more aromatic C-H bonds to form one or more phenols; and purifying the one or more phenols.
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Page/Page column 10
(2014/10/15)
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- A general electron transfer reduction of lactones using SmI 2-H2O
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Herein we describe a strategy for the selective, electron transfer reduction of lactones of all ring sizes and topologies using SmI 2-H2O and a Lewis base to tune the redox properties of the complex. The current protocol permits instantaneous reduction of lactones to the corresponding diols in excellent yields, under mild reaction conditions and with useful chemoselectivity. We demonstrate the broad utility of this transformation through the reduction of complex lactones and sensitive drug-like molecules. Sequential electron transfer reactions and syntheses of deuterated diols are also described.
- Szostak, Michal,Collins, Karl D.,Fazakerley, Neal J.,Spain, Malcolm,Procter, David J.
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supporting information; experimental part
p. 5820 - 5824
(2012/08/28)
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- Preparation of samarium(II) iodide: Quantitative evaluation of the effect of water, oxygen, and peroxide content, preparative methods, and the activation of samarium metal
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Samarium(II) iodide (SmI2) is one of the most important reducing agents in organic synthesis. Synthetic chemistry promoted by SmI2 depends on the efficient and reliable preparation of the reagent. Unfortunately, users can experience difficulties preparing the reagent, and this has prevented realization of the full synthetic potential of SmI2. To provide synthetic chemists with general and reliable methods for the preparation of SmI2, a systematic evaluation of the factors involved in its synthesis has been carried out. Our studies confirm that SmI2 is a user-friendly reagent. Factors such as water, oxygen, and peroxide content in THF have little influence on the synthesis of SmI2. In addition, the use of specialized glovebox equipment or Schlenk techniques is not required for the preparation of SmI2. However, our studies suggest that the quality of samarium metal is an important factor and that the use of low quality metal is the main cause of failed preparations of the reagent. Accordingly, we report a straightforward method for activation of "inactive" samarium metal and demonstrate the broad utility of this protocol through the electron transfer reductions of a range of substrates using SmI2 prepared from otherwise "inactive" metal. An investigation into the stability of SmI2 solutions and an evaluation of commercially available solutions of the reagent is also reported.
- Szostak, Michal,Spain, Malcolm,Procter, David J.
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experimental part
p. 3049 - 3059
(2012/06/01)
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- SYNTHETIC METHODS
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New strategies for the synthesis of salicylaldehyde derivatives having utility production of catalytic metal complexes.
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Page/Page column 42
(2012/06/16)
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- Electron transfer reduction of unactivated esters using SmI 2-H2O
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The reduction of unactivated esters using samarium diiodide is reported for the first time. The optimised protocol allows for the reduction of primary, secondary and tertiary alkyl esters in excellent yields and is competitive with reductions mediated by metal hydrides and alkali metals.
- Szostak, Michal,Spain, Malcolm,Procter, David J.
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supporting information; experimental part
p. 10254 - 10256
(2011/10/31)
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- Biotransformation of dihydrocoumarin by Aspergillus niger ATCC 11394
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Aspergillus niger ATCC 11394 was used to catalyze the biotransformation of dihydrocoumarin using two experimental conditions: growing and resting cells. Six biotransformation products (2- 7) were purified from the bio-reaction media and their structures e
- Aguirre-Pranzoni, Celeste B.,Furque, Gabriela I.,Ardanaz, Carlos E.,Pacciaroni, Adriana,Sosa, Virginia,Tonn, Carlos E.,Kurina-Sanz, Marcela
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experimental part
p. 170 - 181
(2011/05/17)
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- An improved bouveault-blanc ester reduction with stabilized alkali metals
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Significantly improved Bouveault-Blanc conditions for ester reduction have been developed using sodium in silica gel (Na-SG), a free-flowing powder that can be easily handled in the open atmosphere. Primary alcohols were prepared in excellent yield from a variety of aliphatic esters under mild reaction conditions. The chemistry presented here is far safer than the classic Bouveault-Blanc reduction and is competitive with more modern hydride reduction methods.
- Bodnar, Brian S.,Vogt, Paul F.
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supporting information; experimental part
p. 2598 - 2600
(2009/08/07)
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- Intramolecular radical cyclizations onto quinones. A direct synthesis of Bauhinoxepin J
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Bauhinoxepin J has been synthesized in four steps using an intramolecular persulfate-mediated radical addition to a quinone as the key step.
- Kraus, George A.,Thite, Aniket,Liu, Feng
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scheme or table
p. 5303 - 5304
(2009/12/06)
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- Stable isotope characterization of the ortho-oxygenated phenylpropanoids: Coumarin and melilotol
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The natural abundance 2H NMR spectra of extractive coumarin 10 and of its dihydroderivative melilotol 11 produced by baker's yeast reduction has been compared with synthetic materials. Diagnostic for the differentiation of 10 are the (D/H)β values, which are in the 128.1-133.6 ppm interval for the natural compounds but 258.5 and 189.8 ppm for the synthetic materials. Such a dramatic difference is also found for methyl cinnamate 12, which shows (D/H)β values of 127.2 and 515.8 ppm, respectively. In extractive 10, the ratio (D/H)4(para)/(D/H)6(ortho) = 1.24 is similar to that observed in structurally related salicin and methyl salicylate. Coumarin 10 is transformed in salicyl alcohol 9, providing diacetate 14, showing in the natural series the trend (D/H)3(meta) > (D/H)4(para) > (D/H)5(meta) ~ (D/H) 6(ortho). A similar trend is shown also by the synthetic 10. A clear distinction between extractive and synthetic 10 is obtained through δ18O determinations on 10 and on chroman 13. The bulk δ18O values in the extractive series of 10 are 20.3, 23.6, and 22.6‰, while those of the aromatic oxygen are 2.3, 0.5, and -0.5‰. In the synthetic sample, the values are 12.6 and 5.6‰, respectively. As a final product, the reduction of 10 leads to the dihydroderivative 11. Both the baker's yeast reduction and the catalytic hydrogenation lead to a marked decrease of the deuterium content of 11, which is stronger for the β-position than for the α-position.
- Brenna, Elisabetta,Fronza, Giovanni,Fuganti, Claudio,Gatti, Francesco G.,Grande, Valentina,Serra, Stefano,Guillou, Claude,Reniero, Fabiano,Serra, Francesca
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p. 9383 - 9388
(2007/10/03)
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- NMR relaxometric study of new Gd(III) macrocyclic complexes and their interaction with human serum albumin.
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Five novel Gd(iii) complexes based on the structure of the heptadentate macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand have been synthesized and their (1)H and (17)O NMR relaxometric properties investigated in detail. The co
- Botta, Mauro,Quici, Silvio,Pozzi, Gianluca,Marzanni, Giovanni,Pagliarin, Roberto,Barra, Serena,Geninatti Crich, Simonetta
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p. 570 - 577
(2007/10/03)
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- Multidentate phosphite ligands, catalytic compositions containing such ligands, and catalytic prosses utilizing such catalytic compositions
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Multidentate phosphite ligands are disclosed for use in reactions such as hydrocyanation and isomerization. The catalyst compositions made therefrom and the various catalytic processes which employ such multidentate phosphite ligands are also disclosed. I
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- Synthesis of Furo[2,3b]furans and Furo[2,36]pyrans via rhodium-catalyzed tandem hydroformylation/acetalization
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Chemical equation presented Rhodium-catalyzed tandem hydroformylation/acetalization of α,ω-alkenediols gives facile access to perhydrofuro[2,3b]furans and perhydrofuro-[2,3b]pyrans in good yields. Similarly, benzoannelated tetrahydrofuro[2,3b]furans are o
- Roggenbuck, Rafael,Schmidt, Andreas,Eilbracht, Peter
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p. 289 - 291
(2007/10/03)
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- Palladium-catalyzed addition of alcohol pronucleophiles to alkylidenecyclopropanes
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Palladium-catalyzed addition of alcohol pronucleophiles 1 to alkylidenecyclopropane derivatives afforded the corresponding allylic ethers 3 in excellent to moderate yields. Catalyst optimization indicated the Pd(PPh3)4-P(o-tolyl)3 combination as the best system among all catalysts tested. Intramolecular reaction also proceeded smoothly. A plausible mechanism for this catalytic reaction was proposed.
- Camacho,Nakamura,Saito,Yamamoto
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p. 270 - 275
(2007/10/03)
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- KF-Al2O3 is an efficient solid support reagent for the acetylation of amines, alcohols, and phenols. Impeding effect of solvent on the reaction rate
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KF-Al2O3 brings about rapid acetylation of a range of amines, alcohols, and phenols with Ac2O/AcCl. Aliphatic alcohols are acetylated chemoselectively in the presence of phenols. 1° alcohols react several times faster than 2° alcohols. 3° alcohols do not react.
- Yadav, Veejendra K,Ganesh Babu,Mittal, Manish
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p. 7047 - 7051
(2007/10/03)
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- Synthesis of arylalkylmonofluorophosphonates as myo-inositol monophosphatase ligands
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Arylalkylmonofluorophosphonates were prepared by condensation of arylalkylaldehydes with the lithium salt of diethyl 1-fluore-1- (trimethylsilyl)-methylphosphonate. Reduction and hydrolysis sequences gave the final products. These compounds do not inhibit
- Schmitt, Laurent,Cavusoglu, Nukhet,Spiess, Bernard,Schlewer, Gilbert
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p. 4009 - 4012
(2007/10/03)
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- Novel cyclodehydration reaction of hydroxyphenols. An alternative to the Mitsunobu reaction
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A mild, efficient and stereospecific intramolecular process for converting hydroxyphenols into benzodioxanes, dihydrobenzopyrans and dihydrobenzofurans via imidate esters is described. The only by-products are N,N-dimethylformamide and triethylamine hydrochloride which are removed by aqueous work-up making this process highly amenable to large scale operation.
- Procopiou, Panayiotis A.,Brodie, Alastair C.,Deal, Martyn J.,Hayman, David F.,Smith, Gary M.
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p. 2249 - 2256
(2007/10/03)
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- Calcium metal in liquid ammonia for selective reduction of organic compounds
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Selective reduction of functional groups by use of dissolving calcium metal was performed, and the results are in comparison with those by lithium and sodium metals. Reduction with 2.0-2.2 equiv of calcium led chromone (1) to 4-chromanone (2, 75% yield), coumarin (4) to dihydrocoumarin (5, 76% yield) and 3-(2-hydroxyphenyl)-1-propanol (6, 6% yield), α-tetralone (7) to 1,2,3,4-tetrahydro-1-naphthol (8, 81% yield), and β-methoxystyrene (12) to methyl phenethyl ether (13, 85% yield). Performance of reductions on the same substrates by use of 4.0 equiv of lithium or sodium metal gave over-reduced products. Reduction of indole-3-carboxaldehyde (15) to 3-indolemethanol (16), 1-acetylnaphthalene (17) to 1-acetyl-3,4-dihydronaphthalene (18), and trans-4-phenyl-3-buten-2-one (19) to 4-phenyl-2-butanone (20) were accomplished by use of calcium, lithium, and sodium metals, among which calcium gave the highest yields (80-90%). Being a milder reducing agent than lithium and sodium, calcium metal in liquid ammonia offered a better selectivity.
- Hwu, Jih Ru,Wein,Leu, Yi-Jing
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p. 1493 - 1498
(2007/10/03)
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- Selective enzymatic hydrolysis of phenolic acetates
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Phenolic acetates are selectively hydrolyzed in the presence of alkyl acetates, methyl esters and cinnamates with pig liver acetone powder (PLAP).
- Basavaiah,Raju
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p. 467 - 473
(2007/10/02)
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- CHROMENES AND CHROMANONES. PART 1 THE BIRCH REDUCTION OF COUMARINS AND 2H-CHROMENES
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The reduction of coumarin, 4-methylcoumarin, 2,2-dimethyl-2H-chromene and 2,2,4-trimethyl-2H-chromene with sodium or lithium in liquid ammonia with the presence or without donor of protons was carried out.The formation of phenolic products was observed wh
- Aniol, Miroslaw,Lusiak, Przemyslaw,Wawrzenczyk, Czeslaw
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p. 991 - 1000
(2007/10/02)
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- Syntheses and Photophysical Properties of Some 5(2)-Aryl-2(5)-(4-pyridyl)oxazoles and Related Oxadiazoles and Furans
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A number of 5-aryl-2-(4-pyridyl)oxazoles, a 2-aryl-5-(4-pyridyl)oxazole, the related oxadiazole and furan, several 2-(4-pyridyl)cycloalkanooxazoles, and many of their quaternary salts were prepared.No single standard synthesis was effective for preparation of more than a few of the 25 free bases described; methods often unique to a base were employed.Minor variations in structure sometimes produced large differences in absorption and emission wavelengths, as well as in the magnitude of the extinction coefficient.The salts are of interest as laser dyes, scintillation fluors, biological stains, and shifters for luminescent solar concentrators.
- Hall, J. Herbert,Chien, Joseph Yuming,Kauffman, Joel M.,Litak, Peter T.,Adams, Jeffrey K.,et al.
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p. 1245 - 1273
(2007/10/02)
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- The Lactonization of 2'-Hydroxyhydrocinnamic Acid Amides: A Potential Prodrug for Amines
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The lactoniaztion of two hydroxy amides - 4-methoxyaniline 3-(2'-hydroxyphenyl)-3,3-dimethylpropionic acid amide (2b) and 4-methoxyaniline 3-(2'-hydroxy-4',6'-dimethylphenyl)-3,3-dimethylpropionic acid amide (3b) - was studied over a pH range of 1-8.Due to the slowness of its reaction, a third hydroxy amide - 4-methoxyaniline 3-(2'-hydroxyphenyl)propionic acid amide (1b) - was investigated only at pH values of 7.5 and 10.The lactonization of 2b and 3b, which was found to be subject to general catalysis by buffer components, was observed to be catalyzed concurrently but not concertedly by both the acidic and basic forms of the buffer.The buffer-independent pH rate profiles for the lactonization of 2b and 3b were found to obey the equation k0 = kH++> + kH2O + kOH-->, indicating that the reaction is also subject to specific catalysis by hydronium and hydroxide ions.A Broenstedt analysis of the rate constants for buffer catalysis gave α and β values of 0.30 +/- 0.02 and 0.54 +/- 0.04, respectively, for 3b.The rate constants for the accelerated lactonization of 1b at 50, 70, and 90 deg C and pH 10 were used to calculate values of 14.7 +/- 0.8 kcal/mol and -9.5 +/- 2.3 eu for the activation parameters, ΔH(excit.) and ΔS(excit.), respectively.Comparison of the observed rates of lactonization at pH 7.5 and 30 deg C for the three hydroxy amides allowed an estimate of the extent of rate enhancement provided by addition of a partial or total "trimethyl lock" for the hydroxy amide lactonization reaction under near physiological conditions.The order of reactivity of the three hydroxy amides was found to be 3b >> 2b > 1b with rate enhancement factors of 2.5E4, 44, and 1, respectively.This study was begun with the objective of generating a hydroxy amide of very high reactivity at physiological pH for development into amine prodrug forms. 3b, which exhibited a half-life of 65 s at pH 7.5, has been chosen for further development as an amine prodrug.
- Amsberry, Kent L.,Borchardt, Ronald T.
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p. 5867 - 5877
(2007/10/02)
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- The thermodynamic properties of chroman and isochroman
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Measurements leading to the calculation of the ideal-gas thermodynamic properties for chroman and isochroman are reported.Thermochemical and thermophysical properties were determined by adiabatic heat-capacity calorimetry, combustion calorimetry, comparat
- Chirico, R. D.,Archer, D. G.,Hossenlopp, I. A.,Nguyen, A.,Steele, W. V.,Gammon, B. E.
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p. 665 - 682
(2007/10/02)
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- Quinuclidyl benzoxepins as 5-HT3 antagonists
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Certain specific substituted 9-N-(1-azabicyclo-[2.2.2.]octan-3-yl)carboxamido-2,3,4,5-tetrahydro-1-benzoxepins and their valuable use as 5-HT3 antagonists having CNS and gastric prokinetic acticity and void of any significant D2 receptor binding properties are disclosed. Methods for their preparation also are described.
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- 1,2-Regioselective Reduction of α,β-Unsaturated Carbonyl Coumpounds with Lithium Aluminium Hydride in the Presence of Lanthanoid Salts
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An α,β-unsaturated carbonyl compound when reduced by lithium aluminium hydride in the presence of lanthanoid chloride, bromide, iodide, or acetylacetonate gives, selectivity, an allylic alcohol, while in its absence saturated alcohol formation predominates.Such reactions can be applied to various α,β-unsaturated carbonyl compounds such as aldehydes, ketones, esters, and lactones.In addition to its wide applicability, this reagent appears to be easier to use,than other known reducing reagents.
- Fukuzawa, Shin-ichi,Fujinami, Tatsuo,Yamauchi, Shoji,Sakai, Shizuyoshi
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p. 1929 - 1932
(2007/10/02)
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- Aminoborohydrides as Reducing Agents. 1. Sodium (Dimethylamino)- and (tert-Butylamino)borohydrides as Selective Reducing Agents
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Replacement of a hydride in borohydride by an electron-donating alkylamino group greatly enhances the reducing ability of the resulting reagents.Thus, sodium (dimethylamino)- and (tert-butylamino)borohydrides (1, NaDMAB, and 2, NaTBAB, respectively) not only reduce aldehydes and ketones to alcohols but also are effective for the conversion of esters to alcohols and primary amides to amines in good to excellent yields.Tertiary amides are reduced to alcohols (i.e., N,N-dimethylamides) or amines (i.e.N,N-diisopropylamides) depending on the steric bulk of the alkyl substituents on nitrogen.However, secondary amides are not reduced by the reagents allowing selective conversion of primary and tertiary amides in the presence of secondary amides.Nitriles are attacked by the reagents but do not afford synthetically useful amounts of amine products.Aryl halides are slowly converted to arenes, but alkyl halides and epoxides undergo unusual reactions with the amino portion of the reagents.
- Hutchins, Robert O.,Learn, Keith,El-Telbany, Farag,Stercho, Yuriy P.
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p. 2438 - 2443
(2007/10/02)
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- SELECTIVE DEMETHYLATION OF ALIPHATIC METHYL ETHER IN THE PRESENCE OF AROMATIC METHYL ETHER WITH THE ALUMINUM CHLORIDE-SODIUM IODIDE-ACETONITRILE SYSTEM
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A combination system of aluminum chloride-sodium iodide-acetonitrile effects selective demethylation of aliphatic methyl ethers in the presence of aromatic methyl ether.KEYWORDS - demethylation; methyl ether; aluminum chloride; sodium iodide; hard acid; soft nucleophile
- Node, Manabu,Ohta, Keiichiro,Kajimoto, Tetsuya,Nishide, Kiyoharu,Fujita, Eiichi,Fuji, Kaoru
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p. 4178 - 4180
(2007/10/02)
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- Methylase Models: Studies on General-Base vs. Nucleophilic Catalysis in the Intramolecular Alkylation of Phenols
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The ortho substituted phenols, 1 and 3, have been synthesized as models for the O-methylation of catecholamines, as catalyzed by catechol O-methyltransferase.The decomposition of 1 and 3 was studied at 40 deg C over a wide range of pH in both oxyanion and
- Knipe, Jay O.,Vasquez, Peter J.,Coward, James K.
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p. 3202 - 3209
(2007/10/02)
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