- The C-F bond as a tool in the conformational control of amides
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The conformation of 2-fluoro-N-(2-fluoroethyl)-propionamide 4 in the solid state indicates the influence of both a β-fluorine-amide gauche effect and an α-fluoroamide effect. The structure reveals the influence of two recently observed stereoelectronic effects associated with the C-F bond, which has resulted in the successful prediction of the solid state conformation of amide 4. A gauche relationship (-69.9°) was observed for atoms N(1)-C(4)-C(5)-F and a syn planar (2.0°) relationship was observed for N(1)-C(3)-C(2)-F. The paper demonstrates the predictive power of using the C-F bond as a tool in influencing the conformation of amides and peptides.
- Briggs, Caroline R.S.,O'Hagan, David,Howard, Judith A.K.,Yufit, Dmitrii S.
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Read Online
- Silver-catalyzed monofluoroalkylation of heteroarenes with α-fluorocarboxylic acids: an insight into the solvent effect
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A mild and efficient method for direct C-H monofluoroalkylation of heteroarenes with easily accessible and inexpensive α-fluorocarboxylic acids has been developed. This silver-catalyzed reaction affords mono- and bis-monofluoroalkylated heteroarenes in good yields under mild conditions, and the solvent effect on the monofluoroalkylation reaction is discussed in detail.
- Dong, Yunhui,Guo, Chunfang,Han, Xuliang,Li, Xiangye,Li, Xinjin,Li, Yueyun,Liu, Hui,Liu, Zhaolong,Zhang, Lizhi
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supporting information
p. 1147 - 1150
(2022/02/03)
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- Prototypic 18F-Labeled Argininamide-Type Neuropeptide Y Y1R Antagonists as Tracers for PET Imaging of Mammary Carcinoma
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The neuropeptide Y (NPY) Y1 receptor (Y1R) selective radioligand (R)-Nα-(2,2-diphenylacetyl)-Nω-[4-(2-[18F]fluoropropanoylamino)butyl]aminocarbonyl-N-(4-hydroxybenzyl)argininamide ([18F]23), derived from the high-affinity Y1R antagonist BIBP3226, was developed for imaging studies of Y1R-positive tumors. Starting from the argininamide core bearing amine-functionalized spacer moieties, a series of fluoropropanoylated and fluorobenzoylated derivatives was synthesized and studied for Y1R affinity. The fluoropropanoylated derivative 23 displayed high affinity (Ki = 1.3 nM) and selectivity toward Y1R. Radiosynthesis was accomplished via 18F-fluoropropanoylation, yielding [18F]23 with excellent stability in mice; however, the biodistribution study revealed pronounced hepatobiliary clearance with high accumulation in the gall bladder (>100 %ID/g). Despite the unfavorable biodistribution, [18F]23 was successfully used for imaging of Y1R positive MCF-7 tumors in nude mice. Therefore, we suggest [18F]23 as a lead for the design of PET ligands with optimized physicochemical properties resulting in more favorable biodistribution and higher Y1R-dependent enrichment in mammary carcinoma.
- Keller, Max,Maschauer, Simone,Brennauer, Albert,Tripal, Philipp,Koglin, Norman,Dittrich, Ralf,Bernhardt, Günther,Kuwert, Torsten,Wester, Hans-Jürgen,Buschauer, Armin,Prante, Olaf
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supporting information
p. 304 - 309
(2017/03/17)
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- Method for preparing a fluorinated organic compound
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A method for preparing a fluorinated organic compound (II) from an organic compound (I) comprising at least one nucleofugal group Nu, and also a preparation of different specific organic compounds, in particular a fluoro-methylpyrazole compound. The method comprises: a reaction, in the presence of water, of the organic compound (I) and at least one salt providing at least one fluoride anion; and a replacement of at least one nucleofugal group Nu of the compound (I) with a fluorine atom, in order to obtain the fluorinated organic compound (II).
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Paragraph 0293-0294
(2014/06/11)
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- Conformational preference in bis(porphyrin) tweezer complexes: A versatile chirality sensor for α-chiral carboxylic acids
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Metallated porphyrin tweezers have demonstrated a remarkable ability to function as reporters of absolute stereochemistry for a number of different classes of organic molecules. Flexibility in binding, however, can result in an ensemble of different Exciton Coupled Circular Dichroism (ECCD) active conformations that could lead to variable results. Linker flexibility was found to be a key determinant of binding conformation. Experimental results indicate that a balance between linker flexibility and rigidity could yield an optimum porphyrin tweezer that stabilizes a common conformation for all bound chiral guests. This leads to a more simplified approach to absolute stereochemical determination of asymmetry for small organic molecules. This was demonstrated by the use of a C3-linked zincated porphyrin tweezer that yields a common conformational preference for a variety of α-chiral carboxylic acids derivatized with a diamine carrier. Copyright
- Tanasova, Marina,Borhan, Babak
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supporting information; experimental part
p. 3261 - 3269
(2012/07/01)
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- Synthesis and antiviral activity of substituted bisaryl amide compounds as novel influenza virus inhibitors
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The influenza virus is a persistent cause of mortality and morbidity on an annual basis and thus presents itself as an important target for pharmaceutical investigation. In this work, substituted bisaryl amide compounds were found to be a new class of potential anti-influenza agents, and a series of substituted bisaryl amide compounds were synthesised and evaluated for their anti-influenza virus activities. The analysis of the results produced a preliminary structure-activity relationship study (SAR). Compounds 1a, 1g, 1h, 1j, 1l and 1n exhibited clear antiviral activities against the influenza A (A/Guangdong Luohu/219/2006, H1N1) virus with 50% inhibitory concentrations (IC50) for virus growth ranging from 12.5 to 59.0 μM. Specifically, compound 1j also possessed antiviral activity against both oseltamivir-resistant influenza (A/Jinnan/15/2009) virus and influenza B (B/Jifang/13/97) virus with IC 50 values of 9.2 μM and 21.4 μM, respectively. Compound 1j is thus worth further investigation as an anti-influenza virus candidate.
- Hao, Lan-Hu,Li, Yan-Ping,He, Wei-Ying,Wang, Hui-Qiang,Shan, Guang-Zhi,Jiang, Jian-Dong,Li, Yu-Huan,Li, Zhuo-Rong
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p. 117 - 124
(2012/11/07)
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- METHODS OF PREPARING FLUORINATED CARBOXYLIC ACIDS AND THEIR SALTS
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A method for preparing fluorinated carboxylic acids and theirs salts is described comprising subjecting a fluorinated alcohol of the general formula (A): A-CH2-OH to at least one first and at least one second oxidizing agent to produce a highly fluorinated carboxylic acid or their salts of the general formula (B): A-COO M+, wherein M+ represents a cation and wherein A in formulas (A) and (B) is the same and A represents the residue: Rf-[0]p-CX"Y"-[0]m-CX'Y'-[0]n-CXY- wherein Rf represents a fluorinated alkyl residue which may or may not contain one or more catenary oxygen atoms, p, m and n are independently from each other either 1 or O, X, X', X", Y, Y' and Y" are independently from each other H, F, CF3, or C2F5 with the proviso that not all of X, X', X", Y, Y' and Y' ' are H; or A represents the residue: R-CFX- wherein X and R are independently selected from a hydrogen, a halogen, or an alkyl, alkenyl, cycloalkyl, or aryl residue, which may or may not contain one or more fluorine atoms and which may or may not contain one or more catenary oxygen atoms; wherein said at least one first oxidizing agent is a compound that can be converted, by action of the second oxidizing agent, into a reactive species capable of oxidizing the fluorinated alcohol.
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Page/Page column 36-37
(2011/05/06)
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- An unusual conformation of α-haloamides due to cooperative binding with zincated porphyrins
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CD and NMR spectroscopic evidence of cooperative binding between an α-halogen atom and a carboxamide group with a zinc porphyrin leads to an unprecedented conformation for the determination of the absolute stereochemistry of α-haloamides (α-halocarboxylic acids derivatized with 1,4-phenylenediamine) through the use of exciton-coupled circular dichroism (ECCD). With the use of chiral lactams, whose rotomeric contributions are minimized, both ECCD and NMR spectroscopy demonstrate that the porphyrin favors binding to the side of the sterically more demanding halogen atom as compared to the smaller hydrogen atom. In all, the data is strongly suggestive of an unusual conformation not observed before for α-chiral amides. A mnemonic for determining the absolute stereochemistry of α-halogenated carboxylic acids is provided.
- Tanasova, Marina,Yang, Qifei,Olmsted, Courtney C.,Vasileiou, Chrysoula,Li, Xiaoyong,Anyika, Mercy,Borhan, Babak
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supporting information; experimental part
p. 4242 - 4253
(2011/02/25)
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- 3-(2-Acylamino-1-Hydroxyethyl)-Morpholine Derivatives and Their Use as Bace Inhibitors
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The present invention provides BACE inhibitors of Formula (I); methods for their use and preparation, and intermediates useful for their preparation.
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Page/Page column 65
(2008/06/13)
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- A new preparative route to α-fluoroacrylic acid
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Rhodium-catalyzed hydroformylation of vinyl fluoride (VF) followed by careful oxidation of the regiospecifically produced 2-fluoropropanal afforded 2-fluoropropanoic acid (2) in about 70% yield. Dehydrogenation of 2 to α-fluoroacrylic acid (1) was accomplished by a chlorination-dehydrochlorination reaction in more than 60% yield.
- Botteghi,Paganelli,Vicentini,Zarantonello
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p. 113 - 116
(2007/10/03)
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- The enzymatic resolution of an α-fluoroamide by an acylase
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The acylase from Aspergillus melleus was able to hydrolyse the amide bond of (S)-phenylalanine-N-2-(R,S)-fluoropropionamide and discriminate the diastereoisomers such that the (S,S)-diastereoisomer was hydrolysed by an order of magnitude faster than the (S,R)-diasteroisomer. The origin of the kinetic discrimination is attributed to both binding and kinetic effects.
- Banks, John W.,O'Hagan, David
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p. 235 - 238
(2007/10/03)
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- The preferred conformation of α-fluoroamides
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X-Ray structures of two α-fluoroamide derivatives show the O=C-C-F moiety tending towards a trans planar conformation, for which ab initio calculations suggest a deep (up to 8 kcal mol-1) potential minimum.
- Banks, John W.,Batsanov, Andrei S.,Howard, Judith A. K.,O'Hagan, David,Rzepa, Henry S.,Martin-Santamaria, Sonsoles
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p. 2409 - 2411
(2007/10/03)
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- Stereoselective synthesis of 3-fluoro azetidinones via the condensation of 2-fluoropropanethioate lithium enolate with imines
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S-Phenyl-2-fluoropropanethioate (1) was treated with lithium diisopropylamide in THF at -78°C to give rise to the lithium enolate, which underwent stereoselective condensation with a variety of aldehyde imines (2) at room temperature to afford the corresp
- Ishihara,Ichihara,Yamanaka
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p. 255 - 262
(2007/10/02)
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- Simple synthesis of optically active 2-fluoropropanoic acid and analogs of high enantiomeric purity
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A very simple synthesis of optically active 2-fluoropropanoic acid 1 (R=CH3, R′=H) and analogs of high enantiomeric purity was developed using the sulfonates 2 of the corresponding optically active 2-hydroxycarboxylic esters and potassium fluor
- Fritz-Langhals, Elke,Schuetz, Gabi
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p. 293 - 296
(2007/10/02)
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- Synthesis and study of new α-haloacid ferroelectric liquid crystal derivatives. MM2 approach to the molecular structure-ferroelectric activity relationship
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In order to understand the structural factors that influence ferroelectric properties, three new series (F, Cl, and Br) of chiral naphthalene-ring derived compounds were synthesized, and their ferroelectric properties [spontaneous polarization (Ps) and response time (τ)] were evaluated in the pure compound. The chiral tails are α-halo acids derived from L-α-amino acids: L-α-alanine (1), L-leucine (2), L-isoleucine (3), and L-valine (4), with a fluorine, chlorine, or bromine atom in the chiral center. The highest Ps values were obtained for compounds containing a fluorine or chlorine atom in their asymmetric center and with chiral tail derived from L-isoleucine (3) (F-3, 102 nC/cm2; Cl-3, 100 nC/cm2). The steric requirements of the halogen atom and the bulky alkyl group in the asymmetric center determine the most stable conformations of these chiral tails, which have been studied by molecular mechanic empirical calculations, MM2. MM2 calculations prove to be a successful tool for understanding how the structure of the lateral chiral tail affects molecular arrangement and, as a consequence, the ferroelectric properties of the materials.
- Sierra,Serrano,Ros,Ezcurra,Zubía
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p. 7645 - 7651
(2007/10/02)
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- The in situ generation and trapping of some fluorine-substituted ketenes
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Fluoroketene, difluoroketene, methylfluoroketene, trifluoromethylfluoroketene, and phenylfluoroketene were each generated, in situ, via dehydrohalogenation of the respective acid chlorides. In the presence of cyclopentadiene [2 + 2] adducts were obtained in all but the difluoroketene case. In the absence of cyclopentadiene, low temperature 19F nmr indicated the presence of acyl ammonium salts and enolates, potential precursors of the ketenes, but no actual ketene species could unambiguously be detected. The stereochemical results were consistent with the currently accepted steric-based mechanistic rationale for stereochemical determination in ketene cycloadditions.
- Dolbier Jr., William R.,Lee, Suk Kyu,Phanstiel IV, Otto
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p. 2065 - 2072
(2007/10/02)
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- PREPARATION OF MONOFLUOROCARBOXYLIC ACIDS USING N,N-DIETHYL-1,1,2,3,3,3-HEXAFLUOROPROPYLAMINE
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A method is outlined for the preparation of monofluorocarboxylic acids using Ishikawa's reagent, (C2H5)2NCF2CHFCF3 (PPDA), directly from hydroxyesters, or indirectly from monofluorinated alkylbenzenes, followed by the oxidation of the phenyl ring to a carboxylic acid.The chiral fluorocarboxylic acids, (2S) and (2R)-3-fluoro-2-methylpropionates (>99percent ee) and (2S)-2-fluoropropionic acid (55percent ee) are prepared as are 3-fluoropropionate and 4-fluorobutyrate.
- O'Hagan, D.
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p. 371 - 378
(2007/10/02)
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- THE TRANSFORMATION OF α-AMINOACIDS INTO FLUOROACIDS
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The reactions of some α-aminoacids with excess sodium nitrite in polyhydrogen fluoride-pyridine are described.
- Barber, Jill,Keck, Rolf,Retey, Janos
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p. 1549 - 1552
(2007/10/02)
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- Synthetic Methods and Reactions. Part 106. Suppression of Anchimerically Assisted Rearrangement Products in the Synthesis of α-Fluorocarboxylic Acids from α-Amino Acids with 48:52 (w/w) Hydrogen Fluoride/Pyridine
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Anchimerically assisted rearrangement, observed in the fluorination of some α-amino acids with 70:30 (w/w) hydrogen fluoride/pyridine (by weight) in the presence of NaNO2, is substantially or fully suppressed by using the less acidic reagent 48:52 (w/w) hydrogen fluoride/pyridine.
- Olah, George A.,Prakash, G. K. Surya,Chao, Yah Li
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p. 2528 - 2530
(2007/10/02)
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- Stereospezifische 1,2-Wanderungen von Hydroxyl-, Aryl- und Alkylgruppen bei der Nitrosierung von Aminosaeuren in Fluorowasserstoff/pyridin
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The nitrosation of α-amino acids in hydrogenfluoride/pyridine was reinvestigated.In contrast to recent reports it was found that this reaction takes place either with entire (phenylalanine, tyrosine, threonine) or partial (valine, isoleucine) rearrangement to yield β-fluorocarboxylic acids.Glycine, alanine and α-amino-butanoic acid were converted exclusively into the α-fluorocarboxylic acids.The substitution of the amino group takes place with stereochemical retention as revealed by NMR. examination of the 2-fluoro-3-methylpentanoic acids obtained from L-isoleucine and D-alloisoleucine, respectively.
- Keck, Rolf,Retey, Janos
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p. 769 - 772
(2007/10/02)
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