- Silica Subsurface Amine Effect on the Chemical Stability and Chromatographic Properties of End-Capped Immobilized Artificial Membrane Surfaces
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The silica surface of immobilized artificial membranes containing phosphatidylcholine (IAM.PC) has approximately two aminopropyl groups per immobilized phosphatidylcholine molecule.Primary amines near the silica subsurface adsorb biomolecules and also decrease the chemical stability of IAM.PC surfaces.Consequently, subsurface amines were end-capped by several methods including silylating reagents, acetyl analogues, glycidol, methyl glycolate, short-chain anhydrides (3-6 carbons/anhydride chain), and long-chain anhydrides (10-12 carbons/anhydride chain).All end-capping reactions resulted in loss of the initially immobilized phosphatidylcholine molecule.However, the amount of PC loss during end capping was very low (for alkyl anhydride end-capping reactions).After end capping, IAM.PC showed increased chemical stability compared to non end-capped IAM.PC surfaces.The chemical stability of IAM packing material was monitored by phospholipid leaching from IAM surfaces exposed to organic and aqeous solvents using thin-layer chromatography, 1H-NMR spectroscopy, infrared spectroscopy, and mass spectroscopy.IAM.PC packing material end capped with long-chain anhydrides exhibited the greatest chemical stability, i. e., little or no detectable phospholipid leaching when challenged with aqueous and/or organic solvents.The chromatography of acidic and basic compounds of end-capped and non end-capped IAM.PC surfaces was studied.Compared to non end-capped IAM.PC HPLC columns, the chromatographic retention times of acidic compounds (deoxynucleotides) decreased after end caping.In contrast, the retention times of basic compounds (amphetamine analogues) increased on end-capped IAM.PC HPLC columns.This indicates that these solutes have access to the silica subsurface amine during chromatography.
- Invergo, Ben,Alvarez, Francisco M.
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- Differentiation of Nucleophilic and General Base Catalysis in the Hydrolysis of N-Acetylbenzotriazole Using the Proton Inventory Technique
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The hydrolysis of N-acetylbenzotriazole is catalyzed by acetate and imidazole by two different modes as shown by the proton inventory technique.Acetate acts as a general base catalyst to abstract a proton from the attacking water molecule.The unexpected upward curvature in the proton inventory plot can be attributed to a reactant-state isotopic fractionation factor contribution from acetate ion.The proton inventory for imidazole catalysis exhibits downward curvature and is shown to be consistent with a nucleophilic catalyses role for imidazole.The intermediate, 1-acetylimidazole, then undergoes rate-determining water-catalyzed hydrolysis via the expected mechanism.
- Gopalakrishnan, Ganesa,Hogg, John L.
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Read Online
- Synthesis, characterization and spectroscopic studies of two new 1-acetyl-3-alkylimidazolium ionic liquids
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Two new functionalized ionic liquids, 1-acetyl-3-alkylimidazolium iodides, were synthesized by the reactions of 1-acetylimidazole with alkyl iodides under solvent-free condition. Their structures were confirmed by 1H NMR, ESI-MS, IR, UV-Vis and elemental analysis. The 1-acetyl-3-ethylimidazolium iodide (3a) is a solid and 1-acetyl-3-hexylimidazolium iodide (3b) is a viscous liquid at room temperature.
- Huanhuan, Xu,Wenjuan, Zhu,Pingmei, Wang,Dafei, Wang,Qiang, Li
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Read Online
- DNA AFFINITY CLEAVING SEQUENCE SPECIFIC CLEAVAGE OF DNA BY DISTAMYCIN-EDTA*Fe(II) AND EDTA-DISTAMYCIN*Fe(II)
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The attachment of EDTA*Fe(II) to distamycin changes the sequence specific DNA binding antibiotic into a sequence specific DNA cleaving molecule.We report the synthesis of EDTA-distamycin (ED) which has the metal chelator, EDTA, tethered to the carboxy terminus of the N-methylpyrrole tripeptide moiety of the antibiotic, distamycin.EDTA-distamycin*Fe(II) (ED*Fe(II)) at 1E-6M concentration efficiently cleaves pBR322 DNA (1E-5M in base pairs) in the presence of oxygen and dithiothreitol (DTT).Using Maxam-Gilbert sequencing gel analyses, we find that ED*Fe(II) affords DNA cleavage patterns of unequal intensity covering two to four contiguous base pairs adjacent to a five base pair site consisting of adenines (A) and thymines (T).The multiple cleavages at each site might be evidence for a diffusible oxidizing species, perhaps hydroxyl radical.The unequal intensity of cleavage on each side of the A + T site permit assignment of major and minor orientations of the tripeptide binding unit.A comparison of the cleavage specificity of ED*Fe(II) with distamycin-EDTA*Fe(II), (DE*Fe(II)) which has EDTA*Fe(II) attached to the amino terminus of the N-methylpyrrole tripeptide, shows DNA cleavage patterns at the same sites but with intensities of opposite polarity.Maxam-Gilbert sequencing gel analysis of the DNA cleavage patterns by ED*Fe(II) and DE*Fe(II) on both DNA strands of a 381 base pair restriction fragment reveals asymmetric DNA cleavage patterns.Cleavage is shifted to the 3' side of each DNA strand.A model consistent with this cleavage pattern indicates one preferred binding site for ED*Fe(II) and DE*Fe(II) is 3'-TTTAA-5' with the "amino end" of the tripeptide oriented to the 3' end of the thyamine rich strand.This "DNA affinity cleavage" method which consists of attaching cleaving functions to DNA binding molecules followed by DNA cleavage pattern analyses using Maxam-Gilbert sequencing gels may be a useful direct method for determining the binding site and orientation of small molecules on native DNA.
- Taylor, John S.,Schultz, Peter G.,Dervan, Peter B.
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Read Online
- An efficient catalytic method for the c-n acylation of heterocycles by schiff base co(Ii), ni(ii), cu(ii) and zn(ii) transition metal complexes
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The catalytic activity of Schiff base Co(II), Ni(II), Cu(II) and Zn(II) transition metal complexes was tested for N-Acylation of heterocycles with acetyl chloride. It is observed that all the complexes worked as efficient catalysts. The structural type of complexes was studied by an X-ray powder diffractogram (XRD). The mixed ligand complexes with PPh3 ligand show greater activity as compared to Phen complexes and Schiff base complexes. Especially complex [Ni(L)(PPh3)2Cl2] efficiently worked as a catalyst because of high thermal stability (TGA-DSC) and large catalytic surface area (BET).
- Hegade, Sujit,Gaikwad, Gautam,Jadhav, Yuvraj,Chavan, Sanjay,Mulik, Ganpatrao
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p. 611 - 616
(2021/09/30)
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- Facile one-pot synthetic access to libraries of diversely substituted 3-aryl (Alkyl)-coumarins using ionic liquid (IL) or conventional base/solvent, and an IL-mediated approach to novel coumarin-bearing diaryl-ethynes
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The in-situ formed carbonylimidazole derivatives of Ar(alkyl)-CH2COOH react at r.t. with substituted salicylaldehydes in [BMIM][PF6] or [BMIM][BF4] as solvent, and [PAIM][NTf2] as basic-IL, to produce libraries of 3-aryl(alkyl)coumarins. Whereas these reactions can also be performed with similar efficiency in THF by employing DBU, the IL approach offers easier work-up and recycling of the IL solvent. An IL-mediated approach to the synthesis of novel coumarin-bearing diaryl-ethynes by the Sonogshira reaction is also reported, and the potential for recycling/reuse of the IL solvent is shown.
- Kalkhambkar, Rajesh G.,Laali, Kenneth K.,Malunavar, Shruti S.,Prabhala, Pavankumar,Savanur, Hemantkumar M.,Sutar, Suraj M.
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supporting information
(2020/04/08)
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- Length-Selective Synthesis of Acylglycerol-Phosphates through Energy-Dissipative Cycling
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The main aim of origins of life research is to find a plausible sequence of transitions from prebiotic chemistry to nascent biology. In this context, understanding how and when phospholipid membranes appeared on early Earth is critical to elucidating the prebiotic pathways that led to the emergence of primitive cells. Here we show that exposing glycerol-2-phosphate to acylating agents leads to the formation of a library of acylglycerol-phosphates. Medium-chain acylglycerol-phosphates were found to self-assemble into vesicles stable across a wide range of conditions and capable of retaining mono- and oligonucleotides. Starting with a mixture of activated carboxylic acids of different lengths, iterative cycling of acylation and hydrolysis steps allowed for the selection of longer-chain acylglycerol-phosphates. Our results suggest that a selection pathway based on energy-dissipative cycling could have driven the selective synthesis of phospholipids on early Earth.
- Bonfio, Claudia,Caumes, Cécile,Duffy, Colm D.,Patel, Bhavesh H.,Percivalle, Claudia,Tsanakopoulou, Maria,Sutherland, John D.
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supporting information
p. 3934 - 3939
(2019/03/08)
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- Efficient CDI/CH3SO3H-catalyzed, microwave-assisted synthesis of 2-substituted benzothiazoles
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CDI combined with CH3SO3H was found to be highly effective for the cyclization of 2-aminothiophenol derivatives with carboxylic acids under MW condition. Fourteen benzothiazole derivatives were synthesized in good yield and their structures were characterized by1H-NMR,13C-NMR, IR and mass spectrometry. This simple, rapid synthetic method is believed to provide a useful process for the synthesis of 2-substituted benzothiazole compounds.
- Li, Yao-Wei,Zhang, Pei-Ming,Li, Rui,Bai, Yan,Yu, Yu,Gan, Zong-Jie
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supporting information
p. 34 - 39
(2019/05/04)
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- Imidazolium chloride: An efficient catalyst for transamidation of primary amines
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A highly efficient and convenient protocol of imidazolium chloride (30 mol %) catalyzed amidation of amines with moderate to excellent yields was reported. The protocol shows broad substrate scope for aromatic, aliphatic, and heterocyclic primary amines.
- Tian, Qingqiang,Gan, Zongjie,Wang, Xuetong,Li, Dan,Luo, Wen,Wang, Huajun,Dai, Zeshu,Yuan, Jianyong
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supporting information
(2018/09/10)
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- Catalytic Enantioselective Desymmetrization of Norbornenoquinones via C(sp2)-H Alkylation
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The enantioselective Diels-Alder (DA) reaction with monosubstituted p-benzoquinones is an unmet challenge. A new approach for the enantioselective synthesis of monosubstituted quinone-DA adducts is presented based on C(sp2)-H alkylative desymmetrization of meso-DA adducts. Catalyzed by a tertiary amino-thiourea derivative, this reaction utilizes nitroalkanes as the alkylating agents and generates densely functionalized products bearing at least four contiguous stereogenic centers remote from the reaction site with excellent enantioselectivities.
- Sarkar, Rahul,Mukherjee, Santanu
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supporting information
p. 6160 - 6163
(2016/12/09)
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- POLYIMIDE PRECURSOR COMPOSITION AND PREPARATION METHOD AND USE THEREOF
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The present invention provides a polyimide precursor composition comprising a polyimide precursor and a thermal base generator having the structure of formula (1): wherein R1, R2, R3, R4, R5 and are as defined in the specification. The present invention also provides a polyimide prepared from the aforementioned precursor composition, and a preparation method thereof.
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Page/Page column 22
(2016/10/09)
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- Recyclable Hypervalent-Iodine-Mediated Dehydrogenative α,β′-Bifunctionalization of β-Keto Esters under Metal-Free Conditions
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We have developed a method for recyclable hypervalent-iodine-mediated direct dehydrogenative α,β′- bifunctionalization of β-ketoesters and β-diketones under metal-free conditions, which affords a straightforward way to synthesize benzo-fused 2,3-dihydrofurans. This efficient, mild method, which has a wide substrate scope and good functional-group tolerance, was used for the multistep synthesis of the protected aglycone of a naturally occurring phenolic glycoside. A mechanism involving Michael addition to an enone intermediate and subsequent oxidative cyclization is proposed.
- Duan, Ya-Nan,Cui, Li-Qian,Zuo, Lin-Hong,Zhang, Chi
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supporting information
p. 13052 - 13057
(2015/09/07)
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- Microwave-assisted synthesis of 3-nitroindoles from N-aryl enamines via intramolecular arene-alkene coupling
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A variety of N-aryl β-nitroenamines were effectively transformed into 3-nitroindoles in good yields and with complete regioselectivity via a rapid microwave (μW) assisted intramolecular arene-alkene coupling reaction. This report further demonstrates the versatility of this method by constructing 3-carboalkoxy-and 3-cyanoindoles. Optimization data, substrate scope, and applications are discussed.
- Nguyen, Huy H.,Kurth, Mark J.
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p. 362 - 365
(2013/03/13)
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- Bortezomib congeners induce apoptosis of hepatocellular carcinoma via CIP2A inhibition
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CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel compounds and conducted a structure-activity relationship (SAR) study. The results showed that compound 1 was able to repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but with less potency in inhibition of proteasome activity. This finding provides a new direction for the design of CIP2A inhibitors.
- Hou, Duen-Ren,Huang, Ann-Chi,Shiau, Chung-Wai,Wang, Chun-Yi,Yu, Hui-Chuan,Chen, Kuen-Feng
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p. 15398 - 15411
(2014/01/17)
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- BASE GENERATOR
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The present invention provides a base generator having the structure of formula (1): wherein R1, R2, R3, R4, R5, and Y{circle around (?)} are defined as in the specification. The base generator of the present invention can be used for imidization of a polyimide precursor, promoting crosslinking of epoxy monomers, or crosslinking of polyurethane or polyurea.
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Paragraph 0063; 0064
(2013/07/19)
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- CDI-mediated monoacylation of symmetrical diamines and selective acylation of primary amines of unsymmetrical diamines
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A highly efficient and green protocol for monoacylation of symmetrical diamines and chemoselective acylation of primary amines of unsymmetrical diamines has been developed.
- Verma, Sanjeev K.,Ghorpade, Ramarao,Pratap, Ajay,Kaushik
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experimental part
p. 326 - 329
(2012/04/10)
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- Imidazole-catalyzed monoacylation of symmetrical diamines
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Figure Presented. An imidazole-catalyzed protocol for monoacylation of symmetrical diamines has been developed. The protocol gave selective monoacylation of aliphatic (cyclic and acyclic) primary and secondary diamines. In the reaction, imidazole acts as both catalyst and a leaving group. Different monoacylated piperazines and other diamines were synthesized at room temperature in an ethanol/water solvent system.
- Verma, Sanjeev K.,Acharya,Kaushik
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supporting information; experimental part
p. 4232 - 4235
(2010/11/04)
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- Nonactin biosynthesis: Unexpected patterns of label incorporation from 4,6-dioxoheptanoate show evidence of a degradation pathway for levulinate through propionate in Streptomyces griseus
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The polyketide nonactin, a polyketide possessing antitumor and antibacterial activity, is produced by an unusual biosynthesis pathway in Streptomyces griseus that uses both enantiomers of the nonactin precursor, nonactic acid. Despite many studies with labeled precursors, much of the biosynthesis pathway remains unconfirmed, particularly the identity of the last achiral intermediate in the pathway, which is believed to be 4,6-diketoheptanoyl-CoA. We set out to confirm the latter hypothesis with feeding studies employing [4,5-13C2]-, [5,6- 13C2]-, and [6,7-13C2]-4,6- diketoheptanoate thioester derivatives. In each case the isotopic label was incorporated efficiently into nonactin; however, at positions inconsistent with the currently accepted biosynthesis pathway. To resolve the discrepancy, we conducted additional feeding studies with a [3,4-13C 2]levulinate thioester derivative and again observed efficient label incorporation. The latter result was intriguing, as levulinate is not an obvious precursor to nonactin. Levulinate, however, is known to be efficiently degraded into propionate even though the pathway for the conversion is not known. On the basis of both our levulinate and diketoheptanoate isotope incorporation data we can now postulate a pathway from levulinate to propionate that can also account for the conversion of 4,6-diketoheptanoate into levulinate in S. griseus.
- Rong, Jian,Nelson, Micheal E.,Kusche, Brian,Priestley, Nigel D.
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experimental part
p. 2009 - 2012
(2011/03/19)
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- Additive-free chemoselective acylation of amines
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Aliphatic and aromatic amines are efficiently acylated by acetic, pivalic, benzoic, phthalic, or maleic anhydrides in ethyl acetate at room temperature. Under the same experimental conditions, amino alcohols are chemoselectively acylated at the amino group.
- Temperini, Andrea,Terlizzi, Raffaella,Testaferri, Lorenzo,Tiecco, Marcello
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experimental part
p. 295 - 302
(2010/03/30)
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- Mild and useful method for n-acylation of amines
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Iodine is found to promote quantitative N-acylation of primary and secondary amines (aliphatic and aromatic) in a very short time with an equimolar amount of acetyl chloride and benzoyl chloride under solvent-free conditions at room temperature. This catalytic acylation of amines offers an additional useful method for the acetylation using acetyl chloride instead of acetic anhydride and other acetylating agents. This method is also useful in the N-acylation of heterocycles. Mild reaction condition, high selectivity, efficiency, and good yields are some of the major advantages of the procedure.
- Phukan, Kandarpa,Ganguly, Mausumi,Devi, Nirada
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experimental part
p. 2694 - 2701
(2009/12/06)
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- Solvent effects on ester linkage of 4-nitrophenyl acetate in aqueous and ethanol solutions with imidazole and hydroxide ion as nucleophiles
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The reaction of 4-nitrophenyl acetate in aqueous and ethanol solutions with imidazole as a nucleophile has been monitored spectrophotometrically. The second order rate constants of these reactions are 10 times higher in water than in alcoholic solutions. This is attributed to better solvation of the initial state and less solvation of the excited state in the alcohol medium. The entropy of activation in water is more negative indicating the greater structuredness of the excited state in water. In addition to the above, the base hydrolysis reaction of the ester using OH- as a nucleophile in buffered aqueous solutions has been followed spectrophotometrically as a function of pH The observed pseudo first order rate constant obeys the relationship k obs=ko+kOH [OH-] where ko represents the water reactions and the buffer dependent rate constant, and kOH is the rate constant for the OH- catalyzed (specific base) reaction. For both cases, a mechanism involving a tetrahedral intermediate and in which the nucleophile attacks at the electrophillic carbon of the ester C=O is proposed.
- Al-Terairy, Seham S.,Basaif, Salim,El-Awady, Abbas A.
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experimental part
p. 1491 - 1496
(2009/05/15)
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- Mechanistic change in the reactivity of substituted phenyl acetates over phenyl thiolacetates toward imidazole in aqueous phase
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The kinetics of aminolysis of several substituted phenyl acetates by imidazole is studied in aqueous medium at 20°C and an ionic strength of 0.1 M (KCl). By following the leaving groups spectrophotometrically (λ max = 272-401 nm), under excess free imidazole, pseudo-first-order rate constants (κobs) are obtained. For the esters with good nucleofuges, the reaction follows clean second-order kinetics and the plots of (κobs - κH) against free imidazole concentration are linear at constant pH. The macroscopic nucleophilic substitution rate constants (κN) are obtained as the slopes of these plots and found to be pH independent. For the esters with poor nucleofuges, a rate dependence on more than first power of the free imidazole and a linear dependence of κ′2 on free imidazole is observed. Accordingly, the microscopic rate constants for the assisted paths viz. κga and κgb have been disseminated besides for simple bimolecular attack. The Broensted-type plots and Hammett plots were constructed whose slope values are consistent with a stepwise mechanism through a bipolar tetrahedral addition intermediate whose formation or breakdown being rate determining for various paths. Comparison of this reaction of oxyesters with the earlier reported works on similar reaction of analogue thiolesters under identical reaction conditions showed remarkable mechanistic differences which are discussed in detail. The discussion is extended to include the details on previously studied ammonolysis of these two types of esters wherein thiolesters showed differed reactivity than that reported in the present study.
- Rajarathnam,Jeyakumar,Nadar, P. Ananthakrishna
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p. 211 - 221
(2007/10/03)
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- Inhibitors of biotin biosynthesis as potential herbicides
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Isosteric derivatives and analogues of the 7-keto-8-aminopelargonic acid (KAPA), 7,8-diaminopelargonic acid (DAPA) and desthiobiotin (DTB) vitamer intermediates involved in the biosynthetic pathway of biotin were prepared and evaluated as potential herbicides. The most active compound was desmethyl-KAPA which displayed a GR50 (concentration of the active compound that causes a 50% growth inhibition) value of 8 ppm, where values 2 showed moderate activity.
- Nudelman, Ayelet,Marcovici-Mizrahi, Dana,Nudelman, Abraham,Flint, Dennis,Wittenbach, Vernon
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p. 1731 - 1748
(2007/10/03)
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- Biosynthesis of branched-chain fatty acid in bacilli: FabD (malonyl-CoA:ACP transacylase) is not essential for in vitro biosynthesis of branched-chain fatty acids.
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It was found that the partially purified beta-ketoacyl-ACP synthase of Bacillus insolitus did not require the addition of FabD (malonyl-CoA:ACP transacylase, MAT) for the activity assay. This study therefore examined the necessity of FabD protein for in vitro branched-chain fatty acid (BCFA) biosynthesis by crude fatty acid synthetases (FAS) of Bacilli. To discover the involvement of FabD in the BCFA biosynthesis, the protein was removed from the crude FAS by immunoprecipitation. The His-tag fusion protein FabD of Bacillus subtilis was expressed in Escherichia coli and used for the preparation of antibody. The rabbit antibody raised against the expressed fusion protein specifically recognized the FabD in the crude FAS of B. subtilis. Evaluation of the efficacy of the immunoprecipitation showed that a trace of FabD protein was present in the antibody-treated crude FAS. However, this complete removal of FabD from the crude FAS did not abolish its BCFA biosynthesis, but only reduced the level to 50-60% of the control level for acyl-CoA primer and to 80% for alpha-keto-beta-methylvalerate primer. Furthermore, the FabD concentration did not necessarily correlate with the MAT specific activity in the enzyme fractions, suggesting the presence of another enzyme source of MAT activity. This study, therefore, suggests that FabD is not the sole enzyme source of MAT for in vitro BCFA biosynthesis, and implies the existence of a functional connection between fatty acid biosynthesis and another metabolic pathway.
- Oku, Hirosuke,Futamori, Naoya,Masuda, Kenichi,Shimabukuro, Yumiko,Omine, Tomoyo,Iwasaki, Hironori
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p. 2106 - 2114
(2007/10/03)
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- Structure-reactivity correlation in the aminolysis of 4-fluorophenyl acetate in aqueous medium
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The reaction of the title substrate with a series of amines of varying pKa, viz. ammonia, ethanolamine, glycine, 1,2-diaminopropane, 1,3-diaminopropane, n-butylamine, piperidine, hydrazine, imidazole, and hydroxylamine is subjected to a kinetic study in aqueous medium, 25°C, ionic strength 0.1 M (KCl). Pseudo-first-order rate coefficients (kobs) are found throughout under amine excess at various pH values for each amine. For amines, excluding hydrazine, ammonia, and hydroxylamine the reaction follows clean second-order kinetics and the plots of (kobs - kH) against free amine concentration are linear at constant pH. The macroscopic nucleophilic substitution rate coefficients (kN) are obtained as the slopes of these plots and found to be pH independent. For hydrazine, ammonia, and hydroxylamine, a rate dependence on more than first power of the amine is observed, accordingly, the rate constants for the assisted paths have been disseminated for these amines besides kN. The Broensted-type plot (logkN against amine pKa) is linear with a slope value of β = 1.02. The magnitude of the slope value is consistent with a stepwise mechanism through a zwitterionic tetrahedral addition intermediate whose breakdown to products is rate-determining (k2 step). A remarkable reactivity difference is observed among the diamines, the reason for which is discussed in detail.
- Rajarathnam,Jeyakumar,Ananthakrishna Nadar
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p. 366 - 373
(2007/10/03)
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- Nonactin biosynthesis: The initial committed step is the condensation of acetate (malonate) and succinate
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Nonactin is a macrotetrolide antibiotic produced by Streptomyces griseus subsp. griseus ETH A7796 that has shown activity against the P170-glycoprotein efflux pump associated with multiple drug resistant cancer cells. Nonactin is a polyketide, albeit a highly atypical one. The structure is composed of two units of each of the enantiomers of nonactic acid, arranged in a macrocycle, so that the molecule has S4 symmetry and is achiral. The monomer units, (+)- and (-)-nonactic acid, are derived from acetate, succinate, and propionate, although the exact details of the assembly process are quite unclear. We have used feeding experiments with a series of multiple stable isotope labeled precursors to elucidate the details of the first committed step of nonactic acid biosynthesis. We have found that the 13C label from 3-ketoadipate is incorporated specifically into both nonactic acid and its homologue, homononactic acid. The data conclusively show that the first committed step of nonactin biosynthesis is the coupling of a succinate derivative with either acetate or malonate. The differentiation into either nonactate or homononactate occurs after the initial condensation; the homologues are not derived from use of a different "starter unit" by the nonactate polyketide synthase. The first step of nonactin biosynthesis involves achiral intermediates; differentiation between the known enantiocomplementary biosynthesis pathways to form each enantiomer of the precursor monomer units likely occurs after the initial condensation reaction.
- Nelson, Michael E.,Priestley, Nigel D.
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p. 2894 - 2902
(2007/10/03)
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- Synthesis of S-thioacyl dithiophosphates, efficient and chemoselective thioacylating agents
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Easily available acyl dithiophosphates are not stable and isomerise reversibly to O-thioacyl monothiophosphates, especially when subjected to heating. Much slower but probably irreversible isomerisation to S-thioacyl monothiophosphates occurs. Since equilibrium states are established and S-thioacyl (mono)thiophosphates form slowly, reaction mixtures contain generally both thioacylating and acylating agents, and consequently cannot be used for efficient thioacylation. On the other hand, treatment of a mixture of isomeric anhydrides with an excess of a dithiophosphoric acid leads to exclusive formation of S-thioacyl dithiophosphates. They appear to be excellent thioacylating agents: relatively stable, inert towards water and oxygen and therefore easy to handle. Reactions with nitrogen or sulfur nucleophiles proceed very rapidly under ambient conditions, yielding respective thioacyl derivatives. Isolation of the products is very simple. Due to the low reactivity of S-thioacyl dithiophosphates towards oxygen nucleophiles they can be used for direct thioacylation of multifunctional nucleophiles with unprotected hydroxy groups. Respective thioacyl derivatives cannot readily be obtained using other methods.
- Doszczak, Leszek,Rachon, Janusz
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p. 1271 - 1279
(2007/10/03)
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- Linear Bronsted-type behavior in the aminolysis of substituted naphthyl acetates
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The reactions of 4-acetyl-1-naphthyl acetate (1) and 6-acetyl-2-naphthyl acetate (2) with a series of amines of varying pKa, viz. morpholine, ammonia, ethanolamine, glycine, n-butylamine, piperidine, hydrazine, imidazole, and hydroxylamine, are subjected to a kinetic investigation in aqueous medium, 30 °C, ionic strength 0.1 M (KCl). Pseudo-first-order rate coefficients (kobs) are found under amine excess. The plots of (kobs-kH) against free amine concentration are linear at constant pH. The macroscopic nucleophilic substitution rate coefficients (kN) are obtained as the slopes of these plots and found to be pH-independent for all the amines employed. The Bronsted-type plots obtained (log kN against amine pKa) for the aminolysis of both esters 1 and 2 are linear with slope values of β = 0.74 and β = 0.94, respectively. From these values, the kinetic law and the analysis of products, it is deduced that for both esters aminolysis proceed through a zwitterionic tetrahedral addition intermediate (T±) whereby its dissociation into products is rate-limiting (k2 step). Comparison of kN values among them shows that both esters follow an identical mechanistic pathway with 1 having higher reactivity than 2, the reasons for which are discussed.
- Rajarathnam,Ananthakrishna Nadar
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p. 157 - 164
(2007/10/03)
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- An efficient synthesis of mimetics of neamine for RNA recognition.
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As mimetics of neamine, several 4-heterocyclic 2-deoxystreptamine derivatives were chemically synthesized for RNA recognition. Conversion of 4-methylthiomethyl-5,6-di-O-acetyl-diazido-2-deoxystreptamine to the 4-chloromethyl derivative followed by reactions with different nuclophilic reagents gave the 4-heterocyclic 2-deoxystreptamine derivatives in satisfactory yields.
- Ding,Hofstadler,Swayze,Griffey
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p. 1621 - 1623
(2007/10/03)
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- Reactions within Association Complexes: The Reaction of Imidazole with Substituted Phenyl Acetates in the Presence of Detergents in Aqueous Solution
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The bimolecular rate constants for reaction of imidazole with phenyl acetates complexed with sodium dodecyl sulfate (SDS) or cetyltrimethylammonium bromide (CTAB) micelles obey Bronsted equations with βlg similar to that of the reaction in aqueous solution. The dissociation constants of ester (KS) and the hypothetical dissociation constant (KTS) of the transition state of the micelle complexes obey Hansch equations with similar sensitivities (p) to π (-0.66 and -0.589 for KS and -0.735 and -0.495 for KTS, respectively). The slopes also indicate that the microsolvation environments associated with the transition state and the complexed ester have aqueous character. The relative values of KTS and KS indicate that the transition state of the reaction of imidazole with ester is more weakly complexed to both micelles than is the reactant ester. Log KTS values are linear functions of log KS for reactions with both CTAB and SDS; the slopes are, respectively, -0.893 and -1.19 consistent with a slightly more "water-like" medium for the transition state than for the site of binding of ester with CTAB-micelle and slightly less for the SDS-micelle. The results for ester and transition state are consistent with the location of the phenyl residue in a hydrophobic region that possesses water molecules. It is concluded that the acetyl group in the complexed transition state is located in an aqueous part of the Stern region, whereas the phenyl residue is in a part of the Stern region that possesses alkane components. The derived kinetic and complexation parameters in these experiments refer to micelles with Stern regions that have been maintained at constant ionic compositions.
- Pirinccioglu, Necmettin,Zaman, Flora,Williams, Andrew
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p. 2537 - 2543
(2007/10/03)
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- 1,3-Dihydro-1,3-diacetyl-2H-benzimidazol-2-one: A new versatile and selective acetylating agent
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1,3-Dihydro-1,3-diacetyl-2H-benzimidazol-2-one (4, DABI) was proven to be a versatile and selective acetylating agent for amines. Selectivity and reactivity are not only superior than those of other known acetylating agents, but also products could be easily separated with excellent yield.
- Chung, In Hwa,Cha, Ki Suk,Seo, Jae Hong,Kim, Joong Hyup,Chung, Bong Young,Kim, Choong Sup
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p. 529 - 533
(2007/10/03)
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- The selective reaction of primary amines with carbonyl imidazole containing compounds: Selective amide and carbamate synthesis
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matrix presented A new highly selective synthesis of amides and carbamates is described. In both cases the syntheses involve the formation of carbonyl imidazole intermediates which subsequently undergo previously unreported selective reactions with primary amines. Acid imidazolides with sufficient chain length will exclusively react with primary amines even in the presence of secondary and tertiary functionality. The imidazole carboxylic esters of secondary or tertiary alcohols also react selectively with primary amines, forming controlled carbamate structures.
- Rannard, Steve P.,Davis, Nicola J.
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p. 2117 - 2120
(2007/10/03)
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- Investigations on substituent and solvent effects of solvolysis reactions. VIII. The influence of water and nonaqueous solvents on the imidazolysis of 4-nitrophenyl acetate
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The aminolysis reaction of 4-nitrophenyl acetate with imidazole was investigated in water, acetonitrile, propylene carbonate, and 1,4-dioxane at different temperatures, the observed rates can be evaluated with the help of a reaction mechanism consisting of two competitive reaction paths; the first is the bimolecular nucleophilic substitution of the phenol moiety by imidazole; the second path is performed via general base catalysis by a second imidazole molecule. The rate constants of the bimolecular reaction are quantitatively correlated with the four-parameter Taft-Kamlet equation for solvent effects on chemical reactions. A qualitative interpretation of the data shows that the two reaction paths are influenced to the same extent by the solvent.
- Schmeer,Six,Steinkirchner
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p. 211 - 222
(2007/10/03)
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- Synthesis of N-(protected)aminophthalimides: Application to the synthesis of singly labelled isoniazid
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The synthesis of a series of N-(protected)aminophthalimides and the removal of their phthaloyl group leading to N-(protected) or N,N-bis(protected)hydrazines is described. As illustrated by the synthesis of monolabelled isoniazid 3b*, this strategy can be utilized for the preparation of monolabelled substituted hydrazines.
- Brosse, Nicolas,Pinto, Maria-Fatima,Jamart-Gregoire, Brigitte
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p. 3685 - 3688
(2007/10/03)
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- Synthesis, acidity and 19F NMR characteristics of imidazoles bearing 1-fluorinated substituents with potential application as probes for intracellular pH determination.
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A series of 1-substituted imidazoles containing fluorine have been prepared. These compounds were identified as potentially useful probes for intracellular pH determination based on 19F NMR. Key parameters including pK(a), 19F NMR chemical shift sensitivity, water solubility and low toxicity were identified and included in the target molecule selection process. The pK(a) and 19F NMR parameters of the molecules are reported and trends analysed.
- Harper, Jacquie L.,Smith, Robin A. J.,Bedford, Jennifer J.,Leader, John P.
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p. 8211 - 8224
(2007/10/03)
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- N-Cyanazoles in Synthesis of Amides of Carboxylic Acids
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The reaction of carboxylic acids with 1-cyanimidazole, 1-cyanobenzimidazole, and 1-cyano-1,2,4-triazole leads to the formation of 1-acylazoles used in situ in synthesis of anilides of the corresponding carboxylic acids.
- Purygin,Pan'kov
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p. 871 - 873
(2007/10/03)
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- Substituent effects on homolytic bond dissociation free energies of oxygen-acetyl bonds in phenyl acetates and nitrogen-acetyl bonds in acetanilides
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The use of thermochemical cycles makes it possible to determine substituent effects on the homolytic bond dissociation free energies, BDFE, of the oxygen-acetyl bonds in substituted phenyl acetates and the nitrogen-acetyl bonds in substituted acetanilides. A linear correlation between BDFEs for the phenyl acetates and the BDFEs of the oxygen-hydrogen bonds in correspondingly substituted phenols is found with a slope equal to 0.78. An equivalent linear correlation does not exist between the BDFEs of the nitrogen-acetyl bonds in acetanilides and the nitrogen-hydrogen bonds in anilines. This difference in the two correlations of substituent effects on the BDFEs can be explained by the different degrees of stabilization of the parent molecules by the substituents on the phenyl rings. The acetanilides are in this respect extraordinary, since stabilization involving π-resonance plays an important role. Acta Chemica Scandinavica 1996.
- Andersen, Mogens L.
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p. 1045 - 1049
(2007/10/03)
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- Acyl Transfer Mediated by Complexation. The Effect of Cyclodextrins on the Reaction of Nucleophiles with p-Nitrophenyl Acetate and Hexanoate
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The kinetics of the cleavage of p-nitrophenyl acetate (pNPA) and p-nitrophenyl hexanoate (pNPH) by trifluoroethanol (TFE), mercaptoethanol, hydroxylamine or imidazole in the presence of α-cyclodextrin, β-cyclodextrin, or hydroxypropyl-β-cyclodextrin (CDs)
- Tee, Oswald S.,Gadosy, Timothy A.
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p. 2307 - 2312
(2007/10/02)
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- New Tetracyclic Derivatives of Imidazobenzodiazepines and of Imidazothienodiazepines
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The synthesis of new tetracyclic 1,4-diazepine derivatives is described.In these compounds, an additional five-membered heterocycle is fused on the known tricyclic ring systems imidazobenzodiazepine and imidazothienodiazepine.Many of these new compounds display a very high affinity to the benzodiazepine receptor in mammals.
- Gerecke, Max,Kyburz, Emilio,Borer, Rene,Gassner, Walter
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p. 693 - 722
(2007/10/02)
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- PREPARATION OF STERICALLY MORE CROWDED 1,5-DISUBSTITUTED IMIDAZOLES BY THE REGIOSELECTIVE N-ALKYLATION
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4-Substituted 1-acetylimidazoles (6), which were derived from 4(5)-substituted imidazole (1), were N-alkylated by treatment with alkyl halides.During the work-up, the resulting N-alkylated products were easily hydrolyzed into 1,5-disubstituted imidazoles (3).These reactions were regarded to be the general method for the preparation of sterically more crowded 1,5-disubstituted imidazoles (3).
- Kashima, Choji,Harada, Yukari,Hosomi, Akira
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p. 433 - 440
(2007/10/02)
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- Alkylation, Acylation and Silylation of Azoles
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Performing alkylation, acylation and silylation reactions in separate deprotonation and nucleophilic displacement steps allows for better control of reaction conditions and facilitates problem handling in these processes.In the alkylation of azoles the alkylating agents and solvents possess individual reaction capabilities which seem to be approximately additive.Monoalkylation occurs if the sum of the normalized reaction potentials is equal or larger than the pKa value of the azole.Dialkylation is avoided by keeping the sum of the normalized reaction potentials below the pKa value of the alkylazole.The applicability of these principles is demonstrated by the development of effective procedures for the methylation, benzylation, acetylation, methoxycarbonylation and trimethylsilylation of azoles.
- Begtrup, Mikael,Larsen, Peter
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p. 1050 - 1057
(2007/10/02)
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- A New Route to 1,3-Diacyl-2,3-dihydro-1H-imidazoles
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Preparative amounts of the title compounds can be prepared in high purity by hydrogenation of the corresponding 1,3-diacylimidazolium salts with sodium borohydride.Structures are confirmed by spectroscopic methods and in two cases by X-ray structure determination.
- Plath, Martin Wolfgang,Scharf, Hans-Dieter,Raabe, Gerhard,Krueger, Carl
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p. 951 - 955
(2007/10/02)
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- 3-Imidazolium cephalosporin derivatives
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A cephalosporin compound substituted by imidazolium ring in 3-position of cephem having the following formula (I), and pharmaceutically acceptable salt thereof, STR1 wherein R1 is an organic residue known in β-lactam antibiotics, R2 is hydrogen atom or methoxy, n is 0 or 1, A is a nitrogen-containing group constituting imidazolium ring, is useful as an agent for preventing and treating bacterial infections.
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- Chemistry of 1,3,5-Tris(trimethylsiloxy)-1-methoxyhexa-1,3,5-triene, a β-Tricarbonyl Trianion Equivalent
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The title compound has been synthesized and its chemistry studied.Condensation with orthoesters, acid chlorides, or imidazolides gave aromatic compounds in a 5C + 1C condensation.A formal synthesis of lasiodiplodin has been completed.
- Chan, T. H.,Stoessel, D.
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p. 2423 - 2428
(2007/10/02)
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- Selective Thromboxane Synthetase Inhibitors. 1. 1--1H-imidazoles
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1-(2-Phenoxyethyl)-1H-imidazole was found to be an inhibitor of thromboxane (TxA2) synthetase, but it also inhibited the adrenal cytochrome P-450 enzyme steroid 11β-hydroxylase.The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid 11β-hydroxylase is discussed.Potency against TxA2 synthetase was increased by introduction of a carboxyl group at a suitable distance from the imidazole ring.A distance of 8.1-8.8 Angstroem between N-1 of the imidazole and the carboxyl carbon was found to be optimal.Introduction of a carboxyl group also had the effect of reducing activity against steroid 11β-hydroxylase.The most potent and selective compound was found to be 4-benzoic acid (14).
- Cross, Peter E.,Dickinson, Roger P.,Parry, M. John,Randall, Michael J.
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p. 1427 - 1432
(2007/10/02)
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- Anhydrides of Phosphorus and Sulfur Acids, 2. Mixed Anhydrides of Phosphoric, Phosphonic, and Phosphinic Acids with Sulfonic Acids and Sulfuric Monoimidazolide. New Methods of Synthesis, Novel Structures, Phosphorylating Properties
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New applications of methods leading to anhydrides RR'P(O)OSO2R'' (1) are described: a) Reaction of acids RR'P(O)OH (2) with sulfonic imidazolides. b) Reaction of phosphorus imidazolides 4 with sulfonic acids and sulfonic anhydrides.New methods of synthesis of anhydrides 1 have been developed. c) Reaction of phosphorus acid silyl esters RR'P(O)OSiMe3 (9) with methanesulfonic and trifluoromethanesulfonic anhydrides. d) Reaction of bis(trimethylsilyl) tert-butylphosphonate (10) with methanesulfonic acid leading to tBuP(O)(OSO2Me)2 (11). e) Reaction of stannyl phosphate (EtO)2P(O)OSnMe3 (15) with methanesulfonic anhydride. f) Reaction of phosphorus acid silyl esters 9 with trimethylsilyl trifluoromethanesulfonate.All methods result in high yields and can be adapted to a variety of anhydrides 1 derived from phosphoric, phosphonic, and phosphinic acids on the one hand and methanesulfonic, trifluoromethanesulfonic acids and sulfuric monoimidazolide on the other.Phosphonium intermediates have been demonstrated by low temperature FT 31P NMR spectroscopy for reaction b) and c).The anhydrides 1 are readily converted into imidazolides 4 by the reaction with N-(trimethylsilyl)imidazole which proceeds via two distinct phosphonium intermediates.With neutral and weakly basic nucleophiles, the anhydrides 1 behave as phosphorylating agents.
- Dabkowski, Wojciech,Michalski, Jan,Skrzypczynski, Zbigniew
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p. 1809 - 1824
(2007/10/02)
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- Nucleophilic Reactivity toward Acetyl Chloride in Water
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Rate constant ratios for the reactions of acetyl chloride with nucleophilic reagents in water containing 2.5percent (v/v) dioxane were determined by product analysis.The rate constants show a small dependence on the basicity of primary amines, with βnuc=0.25, and are assigned to rate-limiting attack of the nucleophile.Pyridines with pKa>5 behave similarly, with βnuc=0.24, but less basic pyridines react more slowly.Several "α-effect" amines and anionic oxygen nucleophiles show small rate enhancements that are attributed to increases in the rate of nucleophilic attack.The rate constants do not fit the N+ correlation equation, and it is concluded that the reactions of nucleophilic reagents with acyl compounds are not satisfactorily correlated by simple modifications of this equation.
- Palling, David J.,Jencks, William P.
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p. 4869 - 4876
(2007/10/02)
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- SYNTHESIS OF HEPARIN FRAGMENTS. A CHEMICAL SYNTHESIS OF THE TRISACCHARIDE O-(2-DEOXY-2-SULFAMIDO-3,6-DI-O-SULFO-α-D-GLUCOPYRANOSYL)-(1->4)-O-(2-O-SULFO-α-L-IDOPYRANOSYL-URONIC ACID)-(1->4)-2-DEOXY-2-SULFAMIDO-6-O-SULFO-D-GLUCOPYRANOSE HEPTASODIUM SALT
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Known 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose was first converted into methyl 3-O-benzyl-1,2-O-isopropylidene-β-L-idofuranuronate.Acid hydrolysis, followed by acetylation and treatment with titanium tetrabromide, gave methyl (2,4-di-O-acetyl-3-O-benzyl-α-L-idopyranosyl bromide)uronate, which was immediately transformed into methyl 4-O-acetyl-3-O-benzyl-β-L-idopyranuronate 1,2-(tert-butyl orthoacetate).A two-step replacement of the 4-O-acetyl by a 4-O-chloroacetyl group gave the key derivative, crystalline methyl 3-O-benzyl-4-O-chloroacetyl-β-L-idopyranuronate 1,2-(tert-butyl orthoacetate).Condensation of this orthoester with an excess of crystalline benzyl 6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside in chlorobenzene in the presence of 2,6-dimethylpyridinium perchlorate gave crystalline benzyl 6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-4-O-(methyl 2-O-acetyl-3-O-benzyl-4-O-chloroacetyl-α-L-idopyranosyluronate)-α-D-glucopyranoside in 40 percent yield.O-Demonochloroacetylation, followed by condensation with known 3,6-di-O-acetyl-2-azido-4-O-benzyl-2-deoxy-α-D-glucopyranosyl bromide in dichloromethane in the presence of 2,4,6-trimethylpyridine, silver triflate, and molecular sieve provided benzyl O-(3,6-di-O-acetyl-2-azido-4-O-benzyl-2-deoxy-α-D-glucopyranosyl)-(1->4)-O-(methyl 2-O-acetyl-3-O-benzyl-α-L-idopyranosyluronate)-(1->4)-6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside in 88 percent yield.O-Deacetylation with sodium hydroxide, followed successively by O-sulfation in N,N-dimethylformamide in the presence of sulfur trioxide-trimethylamine complex, catalytic hydrogenolysis, and N-sulfation in water with the same sulfating agent, gave the heptasodium salt of O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-α-D-glucopyranosyl)-(1->4)-O-(2-O-sulfo-α-L-idopyranosyluronic acid)-(1->4)-2-deoxy-2-sulfamido-6-O-sulfo-D-glucopyranose.This trisaccharide, which is a fragment of the minimal antithrombin III-binding region in heparin, neither binds to antithrombin III nor induces anti-Xa activity.
- Jacquinet, Jean-Claude,Petitou, Maurice,Duchaussoy, Philippe,Lederman, Isidore,Choay, Jean,et al.
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p. 221 - 242
(2007/10/02)
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